4-78317495-T-C

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.1947T>C(p.His649His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.76 in 1,612,350 control chromosomes in the GnomAD database, including 467,627 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.78 ( 46225 hom., cov: 32)

Exomes 𝑓: 0.76 ( 421402 hom. )

Consequence

FRAS1
NM_025074.7 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -2.44

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=-0.93).

BP6

Variant 4-78317495-T-C is Benign according to our data. Variant chr4-78317495-T-C is described in ClinVar as [Benign]. Clinvar id is 194790.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-78317495-T-C is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-2.44 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.841 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FRAS1	NM_025074.7 link	c.1947T>C	p.His649His	synonymous_variant	Exon 17 of 74	ENST00000512123.4	NP_079350.5	Q86XX4-2
FRAS1	NM_001166133.2 link	c.1947T>C	p.His649His	synonymous_variant	Exon 17 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.1947T>C	p.His649His	synonymous_variant	Exon 17 of 74	5	NM_025074.7	ENSP00000422834.2		Q86XX4-2

Frequencies

GnomAD3 genomes

AF:

0.777

AC:

118084

AN:

152034

Hom.:

46182

Cov.:

show subpopulations

Gnomad AFR

AF:

0.848

Gnomad AMI

AF:

0.817

Gnomad AMR

AF:

0.724

Gnomad ASJ

AF:

0.671

Gnomad EAS

AF:

0.684

Gnomad SAS

AF:

0.595

Gnomad FIN

AF:

0.797

Gnomad MID

AF:

0.642

Gnomad NFE

AF:

0.768

Gnomad OTH

AF:

0.744

GnomAD3 exomes

AF:

0.739

AC:

183163

AN:

247960

Hom.:

68388

AF XY:

0.729

AC XY:

98154

AN XY:

134568

show subpopulations

Gnomad AFR exome

AF:

0.850

Gnomad AMR exome

AF:

0.721

Gnomad ASJ exome

AF:

0.678

Gnomad EAS exome

AF:

0.688

Gnomad SAS exome

AF:

0.590

Gnomad FIN exome

AF:

0.803

Gnomad NFE exome

AF:

0.771

Gnomad OTH exome

AF:

0.731

GnomAD4 exome

AF:

0.758

AC:

1106463

AN:

1460198

Hom.:

421402

Cov.:

AF XY:

0.752

AC XY:

546575

AN XY:

726390

show subpopulations

Gnomad4 AFR exome

AF:

0.846

Gnomad4 AMR exome

AF:

0.720

Gnomad4 ASJ exome

AF:

0.678

Gnomad4 EAS exome

AF:

0.712

Gnomad4 SAS exome

AF:

0.597

Gnomad4 FIN exome

AF:

0.808

Gnomad4 NFE exome

AF:

0.772

Gnomad4 OTH exome

AF:

0.741

GnomAD4 genome

AF:

0.777

AC:

118192

AN:

152152

Hom.:

46225

Cov.:

AF XY:

0.772

AC XY:

57385

AN XY:

74362

show subpopulations

Gnomad4 AFR

AF:

0.848

Gnomad4 AMR

AF:

0.724

Gnomad4 ASJ

AF:

0.671

Gnomad4 EAS

AF:

0.685

Gnomad4 SAS

AF:

0.595

Gnomad4 FIN

AF:

0.797

Gnomad4 NFE

AF:

0.768

Gnomad4 OTH

AF:

0.742

Alfa

AF:

0.756

Hom.:

91900

Bravo

AF:

0.777

Asia WGS

AF:

0.635

AC:

2208

AN:

3478

EpiCase

AF:

0.748

EpiControl

AF:

0.750

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Feb 18, 2015

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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:3

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Mar 05, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

0.0070

DANN

Benign

0.33

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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