4-78438731-T-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_025074.7(FRAS1):c.5366+13T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.36 in 1,566,774 control chromosomes in the GnomAD database, including 105,191 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.31 ( 8434 hom., cov: 33)

Exomes 𝑓: 0.37 ( 96757 hom. )

Consequence

FRAS1
NM_025074.7 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 0.643

Publications

8 publications found

Variant links:

Genes affected

FRAS1 (HGNC:19185): (Fraser extracellular matrix complex subunit 1) This gene encodes an extracellular matrix protein that appears to function in the regulation of epidermal-basement membrane adhesion and organogenesis during development. Mutations in this gene cause Fraser syndrome, a multisystem malformation that can include craniofacial, urogenital and respiratory system abnormalities. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2009]

FRAS1 Gene-Disease associations (from GenCC):

Fraser syndrome
Inheritance: AR Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, ClinGen
Fraser syndrome 1
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
renal agenesis, unilateral
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

FRAS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 4-78438731-T-G is Benign according to our data. Variant chr4-78438731-T-G is described in ClinVar as Benign. ClinVar VariationId is 197083.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.393 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FRAS1	NM_025074.7 link	c.5366+13T>G		intron_variant	Intron 39 of 73	ENST00000512123.4	NP_079350.5	Q86XX4-2
FRAS1	NM_001166133.2 link	c.5366+13T>G		intron_variant	Intron 39 of 41		NP_001159605.1	Q86XX4-5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FRAS1	ENST00000512123.4 link	c.5366+13T>G		intron_variant	Intron 39 of 73	5	NM_025074.7	ENSP00000422834.2		Q86XX4-2

Frequencies

GnomAD3 genomes

AF:

0.312

AC:

47385

AN:

151978

Hom.:

8424

Cov.:

show subpopulations

Gnomad AFR

AF:

0.132

Gnomad AMI

AF:

0.378

Gnomad AMR

AF:

0.401

Gnomad ASJ

AF:

0.332

Gnomad EAS

AF:

0.288

Gnomad SAS

AF:

0.303

Gnomad FIN

AF:

0.436

Gnomad MID

AF:

0.248

Gnomad NFE

AF:

0.383

Gnomad OTH

AF:

0.315

GnomAD2 exomes

AF:

0.376

AC:

71380

AN:

190090

AF XY:

0.372

show subpopulations

Gnomad AFR exome

AF:

0.129

Gnomad AMR exome

AF:

0.479

Gnomad ASJ exome

AF:

0.332

Gnomad EAS exome

AF:

0.313

Gnomad FIN exome

AF:

0.447

Gnomad NFE exome

AF:

0.396

Gnomad OTH exome

AF:

0.356

GnomAD4 exome

AF:

0.365

AC:

517044

AN:

1414678

Hom.:

96757

Cov.:

AF XY:

0.365

AC XY:

255509

AN XY:

700788

show subpopulations

African (AFR)

AF:

0.120

AC:

3820

AN:

31866

American (AMR)

AF:

0.462

AC:

16576

AN:

35896

Ashkenazi Jewish (ASJ)

AF:

0.330

AC:

8369

AN:

25336

East Asian (EAS)

AF:

0.302

AC:

11661

AN:

38600

South Asian (SAS)

AF:

0.306

AC:

24548

AN:

80162

European-Finnish (FIN)

AF:

0.445

AC:

23026

AN:

51770

Middle Eastern (MID)

AF:

0.276

AC:

1569

AN:

5684

European-Non Finnish (NFE)

AF:

0.375

AC:

407704

AN:

1086556

Other (OTH)

AF:

0.336

AC:

19771

AN:

58808

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

15583

31165

46748

62330

77913

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

12698

25396

38094

50792

63490

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.312

AC:

47413

AN:

152096

Hom.:

8434

Cov.:

AF XY:

0.315

AC XY:

23388

AN XY:

74340

show subpopulations

African (AFR)

AF:

0.132

AC:

5472

AN:

41526

American (AMR)

AF:

0.402

AC:

6140

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.332

AC:

1151

AN:

3468

East Asian (EAS)

AF:

0.289

AC:

1494

AN:

5176

South Asian (SAS)

AF:

0.302

AC:

1459

AN:

4824

European-Finnish (FIN)

AF:

0.436

AC:

4597

AN:

10546

Middle Eastern (MID)

AF:

0.243

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.383

AC:

26018

AN:

67964

Other (OTH)

AF:

0.317

AC:

666

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1614

3229

4843

6458

8072

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

476

952

1428

1904

2380

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.349

Hom.:

12450

Bravo

AF:

0.304

Asia WGS

AF:

0.291

AC:

1013

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Mar 11, 2015

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Fraser syndrome 1

Benign:3

Aug 10, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not provided

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

7.7

(source)

DANN

Benign

0.49

PhyloP100

0.64

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over