chr9-20885241-G-A

Variant names:

• chr9-20885241-G-A
• rs2383156
• NM_001375567.1:c.2625+11G>A

Variant summary

Our verdict is Benign. The variant received -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:4
• Conservation: PhyloP100: -0.797
• Publications: 9 publications found

Genes affected

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

FOCAD Gene-Disease associations (from GenCC):

• liver disease, severe congenital

  Inheritance: AR Classification: MODERATE Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -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 VariationId is 402872.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• 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 rank	MANE	Protein	UniProt
FOCAD	NM_001375567.1	c.2625+11G>A		intron_variant	Intron 21 of 43	ENST00000338382.11	NP_001362496.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FOCAD	ENST00000338382.11	c.2625+11G>A		intron_variant	Intron 21 of 43	5	NM_001375567.1	ENSP00000344307.6

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

GnomAD2 exomes AF: 0.588 AC: 109363 AN: 186028 AF XY: 0.586

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 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

African (AFR) AF: 0.590 AC: 16538 AN: 28044

American (AMR) AF: 0.736 AC: 20481 AN: 27836

Ashkenazi Jewish (ASJ) AF: 0.515 AC: 11187 AN: 21710

East Asian (EAS) AF: 0.545 AC: 18774 AN: 34456

South Asian (SAS) AF: 0.610 AC: 35562 AN: 58270

European-Finnish (FIN) AF: 0.594 AC: 28826 AN: 48560

Middle Eastern (MID) AF: 0.642 AC: 3343 AN: 5208

European-Non Finnish (NFE) AF: 0.576 AC: 597958 AN: 1038342

Other (OTH) AF: 0.584 AC: 31197 AN: 53390

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

African (AFR) AF: 0.585 AC: 24199 AN: 41370

American (AMR) AF: 0.669 AC: 10199 AN: 15236

Ashkenazi Jewish (ASJ) AF: 0.514 AC: 1781 AN: 3466

East Asian (EAS) AF: 0.527 AC: 2721 AN: 5164

South Asian (SAS) AF: 0.616 AC: 2961 AN: 4806

European-Finnish (FIN) AF: 0.600 AC: 6304 AN: 10510

Middle Eastern (MID) AF: 0.639 AC: 188 AN: 294

European-Non Finnish (NFE) AF: 0.572 AC: 38852 AN: 67900

Other (OTH) AF: 0.584 AC: 1233 AN: 2110

Alfa AF: 0.542 Hom.: 7990

Bravo AF: 0.592

Asia WGS AF: 0.543 AC: 1886 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jun 14, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

not specified Benign:1

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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
PhyloP100		-0.80
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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