rs10511687

Positions:

Variant summary

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

The NM_001375567.1(FOCAD):c.497T>C(p.Leu166Ser) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.35 in 1,611,422 control chromosomes in the GnomAD database, including 101,775 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.33 ( 8890 hom., cov: 32)

Exomes 𝑓: 0.35 ( 92885 hom. )

Consequence

FOCAD
NM_001375567.1 missense, splice_region

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 2.10

Variant links:

Genes affected

FOCAD (HGNC:23377): (focadhesin) Located in focal adhesion. [provided by Alliance of Genome Resources, Apr 2022]

FOCAD links:

FOCAD (HGNC:):

FOCAD 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=0.0023242235).

BP6

Variant 9-20764871-T-C is Benign according to our data. Variant chr9-20764871-T-C is described in ClinVar as [Benign]. Clinvar id is 402871.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.361 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FOCAD	NM_001375567.1 linkuse as main transcript	c.497T>C	p.Leu166Ser	missense_variant, splice_region_variant	7/44	ENST00000338382.11	NP_001362496.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
FOCAD	ENST00000338382.11 linkuse as main transcript	c.497T>C	p.Leu166Ser	missense_variant, splice_region_variant	7/44	5	NM_001375567.1	ENSP00000344307.6	Q5VW36
FOCAD	ENST00000380249.5 linkuse as main transcript	c.497T>C	p.Leu166Ser	missense_variant, splice_region_variant	9/46	1		ENSP00000369599.1	Q5VW36
FOCAD	ENST00000605031.5 linkuse as main transcript	n.273T>C		splice_region_variant, non_coding_transcript_exon_variant	4/5	4
FOCAD	ENST00000604103.1 linkuse as main transcript	n.290-3T>C		splice_region_variant, intron_variant		4

Frequencies

GnomAD3 genomes

AF:

0.334

AC:

50807

AN:

151928

Hom.:

8888

Cov.:

show subpopulations

Gnomad AFR

AF:

0.322

Gnomad AMI

AF:

0.289

Gnomad AMR

AF:

0.277

Gnomad ASJ

AF:

0.280

Gnomad EAS

AF:

0.0482

Gnomad SAS

AF:

0.367

Gnomad FIN

AF:

0.419

Gnomad MID

AF:

0.350

Gnomad NFE

AF:

0.365

Gnomad OTH

AF:

0.336

GnomAD3 exomes

AF:

0.319

AC:

79962

AN:

250522

Hom.:

14011

AF XY:

0.328

AC XY:

44468

AN XY:

135402

show subpopulations

Gnomad AFR exome

AF:

0.321

Gnomad AMR exome

AF:

0.243

Gnomad ASJ exome

AF:

0.285

Gnomad EAS exome

AF:

0.0419

Gnomad SAS exome

AF:

0.377

Gnomad FIN exome

AF:

0.416

Gnomad NFE exome

AF:

0.355

Gnomad OTH exome

AF:

0.337

GnomAD4 exome

AF:

0.352

AC:

513081

AN:

1459376

Hom.:

92885

Cov.:

AF XY:

0.353

AC XY:

256458

AN XY:

726000

show subpopulations

Gnomad4 AFR exome

AF:

0.320

Gnomad4 AMR exome

AF:

0.250

Gnomad4 ASJ exome

AF:

0.280

Gnomad4 EAS exome

AF:

0.0675

Gnomad4 SAS exome

AF:

0.377

Gnomad4 FIN exome

AF:

0.410

Gnomad4 NFE exome

AF:

0.364

Gnomad4 OTH exome

AF:

0.341

GnomAD4 genome

AF:

0.334

AC:

50836

AN:

152046

Hom.:

8890

Cov.:

AF XY:

0.334

AC XY:

24831

AN XY:

74314

show subpopulations

Gnomad4 AFR

AF:

0.322

Gnomad4 AMR

AF:

0.277

Gnomad4 ASJ

AF:

0.280

Gnomad4 EAS

AF:

0.0483

Gnomad4 SAS

AF:

0.367

Gnomad4 FIN

AF:

0.419

Gnomad4 NFE

AF:

0.365

Gnomad4 OTH

AF:

0.333

Alfa

AF:

0.347

Hom.:

24486

Bravo

AF:

0.320

TwinsUK

AF:

0.358

AC:

1327

ALSPAC

AF:

0.359

AC:

1385

ESP6500AA

AF:

0.322

AC:

1420

ESP6500EA

AF:

0.365

AC:

3143

ExAC

AF:

0.322

AC:

39067

Asia WGS

AF:

0.208

AC:

724

AN:

3478

EpiCase

AF:

0.361

EpiControl

AF:

0.367

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

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	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 14, 2019	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 29, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

FOCAD-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 17, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.055

BayesDel_addAF

Benign

-0.75

BayesDel_noAF

Benign

-0.71

CADD

Benign

DANN

Benign

0.95

Eigen

Benign

-0.68

Eigen_PC

Benign

-0.38

FATHMM_MKL

Benign

0.074

MetaRNN

Benign

0.0023

T;T

MetaSVM

Benign

-0.96

PrimateAI

Uncertain

0.49

PROVEAN

Benign

0.71

N;N

REVEL

Benign

0.069

Sift

Benign

1.0

T;T

Sift4G

Benign

0.90

T;T

Vest4

0.028

MPC

0.0051

ClinPred

0.0034

GERP RS

6.0

gMVP

0.19

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