rs2383156

chr9-20885241-G-Achr9-20885241-G-Cchr9-20885241-G-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001375567.1(FOCAD):c.2625+11G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.581 in 1,467,584 control chromosomes in the GnomAD database, including 248,967 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.59 (26281 hom., cov: 31)
  • Exomes 𝑓: 0.58 (222686 hom.)
• Consequence: FOCAD NM_001375567.1 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.797

Genes affected

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

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BP6: Variant 9-20885241-G-A is Benign according to our data. Variant chr9-20885241-G-A is described in ClinVar as [Benign]. Clinvar id is 402872.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-20885241-G-A is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.659 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FOCAD	NM_001375567.1	c.2625+11G>A		intron_variant		ENST00000338382.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FOCAD	ENST00000338382.11	c.2625+11G>A		intron_variant		5	NM_001375567.1	P1

Frequencies

GnomAD3 genomes AF: 0.587 AC: 88972 AN: 151650 Hom.: 26277 Cov.: 31

Gnomad AFR AF: 0.586

Gnomad AMI AF: 0.623

Gnomad AMR AF: 0.669

Gnomad ASJ AF: 0.514

Gnomad EAS AF: 0.527

Gnomad SAS AF: 0.617

Gnomad FIN AF: 0.600

Gnomad MID AF: 0.633

Gnomad NFE AF: 0.572

Gnomad OTH AF: 0.588

GnomAD3 exomes AF: 0.588 AC: 109363 AN: 186028 Hom.: 32541 AF XY: 0.586 AC XY: 59924 AN XY: 102192

Gnomad AFR exome AF: 0.586

Gnomad AMR exome AF: 0.762

Gnomad ASJ exome AF: 0.517

Gnomad EAS exome AF: 0.503

Gnomad SAS exome AF: 0.612

Gnomad FIN exome AF: 0.591

Gnomad NFE exome AF: 0.563

Gnomad OTH exome AF: 0.590

GnomAD4 exome AF: 0.581 AC: 763866 AN: 1315816 Hom.: 222686 Cov.: 33 AF XY: 0.581 AC XY: 377470 AN XY: 649482

Gnomad4 AFR exome AF: 0.590

Gnomad4 AMR exome AF: 0.736

Gnomad4 ASJ exome AF: 0.515

Gnomad4 EAS exome AF: 0.545

Gnomad4 SAS exome AF: 0.610

Gnomad4 FIN exome AF: 0.594

Gnomad4 NFE exome AF: 0.576

Gnomad4 OTH exome AF: 0.584

GnomAD4 genome AF: 0.586 AC: 89006 AN: 151768 Hom.: 26281 Cov.: 31 AF XY: 0.588 AC XY: 43639 AN XY: 74154

Gnomad4 AFR AF: 0.585

Gnomad4 AMR AF: 0.669

Gnomad4 ASJ AF: 0.514

Gnomad4 EAS AF: 0.527

Gnomad4 SAS AF: 0.616

Gnomad4 FIN AF: 0.600

Gnomad4 NFE AF: 0.572

Gnomad4 OTH AF: 0.584

Alfa AF: 0.542 Hom.: 7864

Bravo AF: 0.592

Asia WGS AF: 0.543 AC: 1886 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 14, 2019	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Feb 01, 2024	- -

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 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
Cadd	Benign	0.63
Dann	Benign	0.68

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

Other links and lift over

dbSNP: rs2383156; hg19: chr9-20885240; COSMIC: COSV58099836;