Variant 4-78464478-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_025074.7(FRAS1):c.6924C>T(p.Val2308=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0736 in 1,613,782 control chromosomes in the GnomAD database, including 5,030 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.055 ( 325 hom., cov: 32)

Exomes 𝑓: 0.075 ( 4705 hom. )

Consequence

FRAS1
NM_025074.7 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 2.79

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 -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.32).

BP6

Variant 4-78464478-C-T is Benign according to our data. Variant chr4-78464478-C-T is described in ClinVar as [Benign]. Clinvar id is 261810.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-78464478-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=2.79 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0819 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FRAS1	NM_025074.7 linkuse as main transcript	c.6924C>T	p.Val2308=	synonymous_variant	49/74	ENST00000512123.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FRAS1	ENST00000512123.4 linkuse as main transcript	c.6924C>T	p.Val2308=	synonymous_variant	49/74	5	NM_025074.7	P1	Q86XX4-2
FRAS1	ENST00000682513.1 linkuse as main transcript	c.6924C>T	p.Val2308=	synonymous_variant	49/64

Frequencies

GnomAD3 genomes

AF:

0.0552

AC:

8393

AN:

152126

Hom.:

326

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0151

Gnomad AMI

AF:

0.0747

Gnomad AMR

AF:

0.0419

Gnomad ASJ

AF:

0.0550

Gnomad EAS

AF:

0.00154

Gnomad SAS

AF:

0.0280

Gnomad FIN

AF:

0.0888

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.0837

Gnomad OTH

AF:

0.0411

GnomAD3 exomes

AF:

0.0575

AC:

14312

AN:

248878

Hom.:

571

AF XY:

0.0582

AC XY:

7851

AN XY:

135002

show subpopulations

Gnomad AFR exome

AF:

0.0117

Gnomad AMR exome

AF:

0.0229

Gnomad ASJ exome

AF:

0.0541

Gnomad EAS exome

AF:

0.000278

Gnomad SAS exome

AF:

0.0286

Gnomad FIN exome

AF:

0.0940

Gnomad NFE exome

AF:

0.0849

Gnomad OTH exome

AF:

0.0536

GnomAD4 exome

AF:

0.0755

AC:

110315

AN:

1461538

Hom.:

4705

Cov.:

AF XY:

0.0742

AC XY:

53939

AN XY:

727068

show subpopulations

Gnomad4 AFR exome

AF:

0.0104

Gnomad4 AMR exome

AF:

0.0244

Gnomad4 ASJ exome

AF:

0.0558

Gnomad4 EAS exome

AF:

0.000378

Gnomad4 SAS exome

AF:

0.0297

Gnomad4 FIN exome

AF:

0.0937

Gnomad4 NFE exome

AF:

0.0862

Gnomad4 OTH exome

AF:

0.0636

GnomAD4 genome

AF:

0.0551

AC:

8391

AN:

152244

Hom.:

325

Cov.:

AF XY:

0.0539

AC XY:

4009

AN XY:

74432

show subpopulations

Gnomad4 AFR

AF:

0.0150

Gnomad4 AMR

AF:

0.0418

Gnomad4 ASJ

AF:

0.0550

Gnomad4 EAS

AF:

0.00154

Gnomad4 SAS

AF:

0.0278

Gnomad4 FIN

AF:

0.0888

Gnomad4 NFE

AF:

0.0837

Gnomad4 OTH

AF:

0.0407

Alfa

AF:

0.0707

Hom.:

590

Bravo

AF:

0.0494

Asia WGS

AF:

0.0110

AC:

AN:

3478

EpiCase

AF:

0.0739

EpiControl

AF:

0.0756

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 31, 2024

- -

Fraser syndrome 1

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.32

CADD

Benign

8.5

DANN

Benign

0.65

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.10

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