rs11098194

Variant names:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_025074.7(FRAS1):c.8439C>T(p.Asp2813Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.361 in 1,576,474 control chromosomes in the GnomAD database, including 106,007 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.33 ( 8800 hom., cov: 33)

Exomes 𝑓: 0.37 ( 97207 hom. )

Consequence

FRAS1
NM_025074.7 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 1.37

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.55).

BP6

Variant 4-78479714-C-T is Benign according to our data. Variant chr4-78479714-C-T is described in ClinVar as [Benign]. Clinvar id is 261815.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-78479714-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=1.37 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.402 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FRAS1	NM_025074.7 link	c.8439C>T	p.Asp2813Asp	synonymous_variant	Exon 56 of 74	ENST00000512123.4	NP_079350.5	Q86XX4-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FRAS1	ENST00000512123.4 link	c.8439C>T	p.Asp2813Asp	synonymous_variant	Exon 56 of 74	5	NM_025074.7	ENSP00000422834.2		Q86XX4-2
FRAS1	ENST00000682513.1 link	c.8439C>T	p.Asp2813Asp	synonymous_variant	Exon 56 of 64			ENSP00000508201.1		A0A804HL50

Frequencies

GnomAD3 genomes

AF:

0.325

AC:

49456

AN:

151998

Hom.:

8789

Cov.:

show subpopulations

Gnomad AFR

AF:

0.178

Gnomad AMI

AF:

0.388

Gnomad AMR

AF:

0.410

Gnomad ASJ

AF:

0.314

Gnomad EAS

AF:

0.302

Gnomad SAS

AF:

0.270

Gnomad FIN

AF:

0.437

Gnomad MID

AF:

0.250

Gnomad NFE

AF:

0.384

Gnomad OTH

AF:

0.328

GnomAD3 exomes

AF:

0.371

AC:

81900

AN:

220760

Hom.:

15888

AF XY:

0.366

AC XY:

43378

AN XY:

118544

show subpopulations

Gnomad AFR exome

AF:

0.169

Gnomad AMR exome

AF:

0.482

Gnomad ASJ exome

AF:

0.309

Gnomad EAS exome

AF:

0.315

Gnomad SAS exome

AF:

0.279

Gnomad FIN exome

AF:

0.443

Gnomad NFE exome

AF:

0.390

Gnomad OTH exome

AF:

0.354

GnomAD4 exome

AF:

0.365

AC:

520352

AN:

1424358

Hom.:

97207

Cov.:

AF XY:

0.363

AC XY:

255628

AN XY:

704030

show subpopulations

Gnomad4 AFR exome

AF:

0.171

Gnomad4 AMR exome

AF:

0.470

Gnomad4 ASJ exome

AF:

0.307

Gnomad4 EAS exome

AF:

0.305

Gnomad4 SAS exome

AF:

0.276

Gnomad4 FIN exome

AF:

0.443

Gnomad4 NFE exome

AF:

0.375

Gnomad4 OTH exome

AF:

0.338

GnomAD4 genome

AF:

0.325

AC:

49496

AN:

152116

Hom.:

8800

Cov.:

AF XY:

0.328

AC XY:

24396

AN XY:

74356

show subpopulations

Gnomad4 AFR

AF:

0.178

Gnomad4 AMR

AF:

0.411

Gnomad4 ASJ

AF:

0.314

Gnomad4 EAS

AF:

0.302

Gnomad4 SAS

AF:

0.270

Gnomad4 FIN

AF:

0.437

Gnomad4 NFE

AF:

0.384

Gnomad4 OTH

AF:

0.331

Alfa

AF:

0.352

Hom.:

5784

Bravo

AF:

0.320

Asia WGS

AF:

0.294

AC:

1025

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Fraser syndrome 1

Benign:3

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. -

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

- -

not specified

Benign:2

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

- -

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

-0.55

CADD

Benign

3.1

DANN

Benign

0.21

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over