rs345513

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_025074.7(FRAS1):c.2060A>G(p.Asp687Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.398 in 1,613,426 control chromosomes in the GnomAD database, including 129,031 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.43 ( 13884 hom., cov: 32)

Exomes 𝑓: 0.40 ( 115147 hom. )

Consequence

FRAS1
NM_025074.7 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: 0.606

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=2.3511052E-4).

BP6

Variant 4-78318909-A-G is Benign according to our data. Variant chr4-78318909-A-G is described in ClinVar as [Benign]. Clinvar id is 261804.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-78318909-A-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.475 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FRAS1	NM_025074.7 link	c.2060A>G	p.Asp687Gly	missense_variant	Exon 18 of 74	ENST00000512123.4	NP_079350.5	Q86XX4-2
FRAS1	NM_001166133.2 link	c.2060A>G	p.Asp687Gly	missense_variant	Exon 18 of 42		NP_001159605.1	Q86XX4-5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FRAS1	ENST00000512123.4 link	c.2060A>G	p.Asp687Gly	missense_variant	Exon 18 of 74	5	NM_025074.7	ENSP00000422834.2		Q86XX4-2

Frequencies

GnomAD3 genomes

AF:

0.425

AC:

64602

AN:

151914

Hom.:

13869

Cov.:

show subpopulations

Gnomad AFR

AF:

0.481

Gnomad AMI

AF:

0.420

Gnomad AMR

AF:

0.428

Gnomad ASJ

AF:

0.435

Gnomad EAS

AF:

0.415

Gnomad SAS

AF:

0.381

Gnomad FIN

AF:

0.424

Gnomad MID

AF:

0.389

Gnomad NFE

AF:

0.395

Gnomad OTH

AF:

0.412

GnomAD3 exomes

AF:

0.412

AC:

102728

AN:

249100

Hom.:

21236

AF XY:

0.406

AC XY:

54905

AN XY:

135124

show subpopulations

Gnomad AFR exome

AF:

0.485

Gnomad AMR exome

AF:

0.457

Gnomad ASJ exome

AF:

0.428

Gnomad EAS exome

AF:

0.424

Gnomad SAS exome

AF:

0.372

Gnomad FIN exome

AF:

0.430

Gnomad NFE exome

AF:

0.394

Gnomad OTH exome

AF:

0.403

GnomAD4 exome

AF:

0.395

AC:

577837

AN:

1461394

Hom.:

115147

Cov.:

AF XY:

0.395

AC XY:

286863

AN XY:

726976

show subpopulations

Gnomad4 AFR exome

AF:

0.482

Gnomad4 AMR exome

AF:

0.456

Gnomad4 ASJ exome

AF:

0.436

Gnomad4 EAS exome

AF:

0.406

Gnomad4 SAS exome

AF:

0.376

Gnomad4 FIN exome

AF:

0.428

Gnomad4 NFE exome

AF:

0.389

Gnomad4 OTH exome

AF:

0.393

GnomAD4 genome

AF:

0.425

AC:

64663

AN:

152032

Hom.:

13884

Cov.:

AF XY:

0.425

AC XY:

31598

AN XY:

74318

show subpopulations

Gnomad4 AFR

AF:

0.480

Gnomad4 AMR

AF:

0.428

Gnomad4 ASJ

AF:

0.435

Gnomad4 EAS

AF:

0.416

Gnomad4 SAS

AF:

0.381

Gnomad4 FIN

AF:

0.424

Gnomad4 NFE

AF:

0.395

Gnomad4 OTH

AF:

0.414

Alfa

AF:

0.396

Hom.:

28044

Bravo

AF:

0.431

TwinsUK

AF:

0.391

AC:

1451

ALSPAC

AF:

0.390

AC:

1503

ESP6500AA

AF:

0.471

AC:

1864

ESP6500EA

AF:

0.383

AC:

3188

ExAC

AF:

0.410

AC:

49525

Asia WGS

AF:

0.390

AC:

1355

AN:

3478

EpiCase

AF:

0.382

EpiControl

AF:

0.384

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

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:3

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 14, 2019

GeneDx

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

- -

Fraser syndrome 1

Benign:3

Jan 12, 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. -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

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

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.57

CADD

Benign

1.6

DANN

Benign

0.068

Eigen

Benign

-0.70

Eigen_PC

Benign

-0.78

FATHMM_MKL

Benign

0.0028

LIST_S2

Benign

0.34

T;T

MetaRNN

Benign

0.00024

T;T

MetaSVM

Benign

-0.90

MutationAssessor

Benign

-1.3

N;N

PrimateAI

Benign

0.24

PROVEAN

Benign

2.3

N;.

REVEL

Benign

0.082

Sift

Benign

1.0

T;.

Sift4G

Benign

0.53

T;T

Vest4

0.023

ClinPred

0.0015

GERP RS

4.0

gMVP

0.31

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

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