rs398092530

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_025074.7(FRAS1):c.3151+14_3151+15dupTG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.361 in 1,561,108 control chromosomes in the GnomAD database, including 103,737 homozygotes. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.38 ( 11138 hom., cov: 0)

Exomes 𝑓: 0.36 ( 92599 hom. )

Consequence

FRAS1
NM_025074.7 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -1.47

Publications

2 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 -16 ACMG points.

BP6

Variant 4-78374264-C-CTG is Benign according to our data. Variant chr4-78374264-C-CTG is described in ClinVar as Benign. ClinVar VariationId is 261806.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.462 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FRAS1	NM_025074.7 link	c.3151+14_3151+15dupTG		intron_variant	Intron 25 of 73	ENST00000512123.4	NP_079350.5
FRAS1	NM_001166133.2 link	c.3151+14_3151+15dupTG		intron_variant	Intron 25 of 41		NP_001159605.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
FRAS1	ENST00000512123.4 link	c.3151+14_3151+15dupTG	intron_variant	Intron 25 of 73	5	NM_025074.7	ENSP00000422834.2
FRAS1	ENST00000325942.11 link	c.3151+14_3151+15dupTG	intron_variant	Intron 25 of 41	1		ENSP00000326330.6
FRAS1	ENST00000682513.1 link	c.3151+14_3151+15dupTG	intron_variant	Intron 25 of 63			ENSP00000508201.1
FRAS1	ENST00000684159.1 link	c.3151+14_3151+15dupTG	intron_variant	Intron 25 of 44			ENSP00000506875.1

Frequencies

GnomAD3 genomes

AF:

0.379

AC:

57478

AN:

151822

Hom.:

11129

Cov.:

show subpopulations

Gnomad AFR

AF:

0.468

Gnomad AMI

AF:

0.277

Gnomad AMR

AF:

0.345

Gnomad ASJ

AF:

0.294

Gnomad EAS

AF:

0.340

Gnomad SAS

AF:

0.224

Gnomad FIN

AF:

0.312

Gnomad MID

AF:

0.354

Gnomad NFE

AF:

0.362

Gnomad OTH

AF:

0.373

GnomAD2 exomes

AF:

0.337

AC:

82353

AN:

244358

AF XY:

0.331

show subpopulations

Gnomad AFR exome

AF:

0.467

Gnomad AMR exome

AF:

0.305

Gnomad ASJ exome

AF:

0.307

Gnomad EAS exome

AF:

0.342

Gnomad FIN exome

AF:

0.313

Gnomad NFE exome

AF:

0.363

Gnomad OTH exome

AF:

0.343

GnomAD4 exome

AF:

0.359

AC:

505254

AN:

1409168

Hom.:

92599

Cov.:

AF XY:

0.354

AC XY:

245645

AN XY:

694690

show subpopulations

African (AFR)

AF:

0.468

AC:

15318

AN:

32706

American (AMR)

AF:

0.309

AC:

13512

AN:

43752

Ashkenazi Jewish (ASJ)

AF:

0.299

AC:

7509

AN:

25072

East Asian (EAS)

AF:

0.343

AC:

13234

AN:

38626

South Asian (SAS)

AF:

0.230

AC:

18526

AN:

80442

European-Finnish (FIN)

AF:

0.315

AC:

16354

AN:

51892

Middle Eastern (MID)

AF:

0.351

AC:

1905

AN:

5434

European-Non Finnish (NFE)

AF:

0.371

AC:

398390

AN:

1073596

Other (OTH)

AF:

0.356

AC:

20506

AN:

57648

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

14590

29180

43769

58359

72949

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

13112

26224

39336

52448

65560

<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:

0.379

AC:

57529

AN:

151940

Hom.:

11138

Cov.:

AF XY:

0.373

AC XY:

27730

AN XY:

74294

show subpopulations

African (AFR)

AF:

0.468

AC:

19349

AN:

41376

American (AMR)

AF:

0.344

AC:

5261

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.294

AC:

1019

AN:

3470

East Asian (EAS)

AF:

0.340

AC:

1758

AN:

5164

South Asian (SAS)

AF:

0.224

AC:

1079

AN:

4814

European-Finnish (FIN)

AF:

0.312

AC:

3291

AN:

10564

Middle Eastern (MID)

AF:

0.367

AC:

108

AN:

294

European-Non Finnish (NFE)

AF:

0.362

AC:

24632

AN:

67960

Other (OTH)

AF:

0.369

AC:

779

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1805

3611

5416

7222

9027

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

542

1084

1626

2168

2710

<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:

0.363

Hom.:

1832

Bravo

AF:

0.386

Asia WGS

AF:

0.291

AC:

1010

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Fraser syndrome 1

Benign:2

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Aug 10, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

-1.5

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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

Publications

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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