Variant 4-78516001-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_025074.7(FRAS1):c.10377C>T(p.Thr3459=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.178 in 1,611,934 control chromosomes in the GnomAD database, including 25,924 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.19 ( 2692 hom., cov: 32)

Exomes 𝑓: 0.18 ( 23232 hom. )

Consequence

FRAS1
NM_025074.7 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -1.67

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=-0.51).

BP6

Variant 4-78516001-C-T is Benign according to our data. Variant chr4-78516001-C-T is described in ClinVar as [Benign]. Clinvar id is 261795.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-78516001-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-1.67 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.221 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FRAS1	NM_025074.7 linkuse as main transcript	c.10377C>T	p.Thr3459=	synonymous_variant	66/74	ENST00000512123.4	NP_079350.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FRAS1	ENST00000512123.4 linkuse as main transcript	c.10377C>T	p.Thr3459=	synonymous_variant	66/74	5	NM_025074.7	ENSP00000422834	P1	Q86XX4-2

Frequencies

GnomAD3 genomes

AF:

0.185

AC:

28199

AN:

152072

Hom.:

2690

Cov.:

show subpopulations

Gnomad AFR

AF:

0.186

Gnomad AMI

AF:

0.134

Gnomad AMR

AF:

0.170

Gnomad ASJ

AF:

0.269

Gnomad EAS

AF:

0.232

Gnomad SAS

AF:

0.141

Gnomad FIN

AF:

0.201

Gnomad MID

AF:

0.259

Gnomad NFE

AF:

0.182

Gnomad OTH

AF:

0.189

GnomAD3 exomes

AF:

0.180

AC:

44314

AN:

246138

Hom.:

4141

AF XY:

0.179

AC XY:

23862

AN XY:

133482

show subpopulations

Gnomad AFR exome

AF:

0.184

Gnomad AMR exome

AF:

0.138

Gnomad ASJ exome

AF:

0.265

Gnomad EAS exome

AF:

0.235

Gnomad SAS exome

AF:

0.143

Gnomad FIN exome

AF:

0.200

Gnomad NFE exome

AF:

0.183

Gnomad OTH exome

AF:

0.173

GnomAD4 exome

AF:

0.177

AC:

258534

AN:

1459744

Hom.:

23232

Cov.:

AF XY:

0.176

AC XY:

127810

AN XY:

725986

show subpopulations

Gnomad4 AFR exome

AF:

0.192

Gnomad4 AMR exome

AF:

0.143

Gnomad4 ASJ exome

AF:

0.261

Gnomad4 EAS exome

AF:

0.212

Gnomad4 SAS exome

AF:

0.144

Gnomad4 FIN exome

AF:

0.205

Gnomad4 NFE exome

AF:

0.175

Gnomad4 OTH exome

AF:

0.191

GnomAD4 genome

AF:

0.185

AC:

28208

AN:

152190

Hom.:

2692

Cov.:

AF XY:

0.186

AC XY:

13859

AN XY:

74408

show subpopulations

Gnomad4 AFR

AF:

0.186

Gnomad4 AMR

AF:

0.169

Gnomad4 ASJ

AF:

0.269

Gnomad4 EAS

AF:

0.232

Gnomad4 SAS

AF:

0.140

Gnomad4 FIN

AF:

0.201

Gnomad4 NFE

AF:

0.182

Gnomad4 OTH

AF:

0.187

Alfa

AF:

0.173

Hom.:

1508

Bravo

AF:

0.183

Asia WGS

AF:

0.207

AC:

721

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

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

-0.51

CADD

Benign

0.28

DANN

Benign

0.45

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