9-20921333-A-G

Variant names:

• chr9-20921333-A-G
• rs12353255
• NM_001375567.1:c.2853-2327A>G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001375567.1(FOCAD):​c.2853-2327A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.628 in 152,042 control chromosomes in the GnomAD database, including 30,525 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.63 (30525 hom., cov: 32)
• Consequence: FOCAD NM_001375567.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.20
• Publications: 3 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.39).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.691 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FOCAD	NM_001375567.1	c.2853-2327A>G		intron_variant	Intron 24 of 43	ENST00000338382.11	NP_001362496.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FOCAD	ENST00000338382.11	c.2853-2327A>G		intron_variant	Intron 24 of 43	5	NM_001375567.1	ENSP00000344307.6
FOCAD	ENST00000380249.5	c.2853-2327A>G		intron_variant	Intron 26 of 45	1		ENSP00000369599.1
FOCAD	ENST00000605086.5	n.1323-2327A>G		intron_variant	Intron 12 of 31	1

Frequencies

GnomAD3 genomes AF: 0.628 AC: 95378 AN: 151924 Hom.: 30485 Cov.: 32

Gnomad AFR AF: 0.520

Gnomad AMI AF: 0.762

Gnomad AMR AF: 0.582

Gnomad ASJ AF: 0.713

Gnomad EAS AF: 0.534

Gnomad SAS AF: 0.698

Gnomad FIN AF: 0.643

Gnomad MID AF: 0.687

Gnomad NFE AF: 0.696

Gnomad OTH AF: 0.654

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.628 AC: 95472 AN: 152042 Hom.: 30525 Cov.: 32 AF XY: 0.624 AC XY: 46370 AN XY: 74302

African (AFR) AF: 0.521 AC: 21578 AN: 41438

American (AMR) AF: 0.582 AC: 8902 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.713 AC: 2476 AN: 3472

East Asian (EAS) AF: 0.534 AC: 2760 AN: 5170

South Asian (SAS) AF: 0.699 AC: 3364 AN: 4814

European-Finnish (FIN) AF: 0.643 AC: 6790 AN: 10568

Middle Eastern (MID) AF: 0.690 AC: 203 AN: 294

European-Non Finnish (NFE) AF: 0.696 AC: 47321 AN: 67976

Other (OTH) AF: 0.656 AC: 1385 AN: 2112

Alfa AF: 0.678 Hom.: 15108

Bravo AF: 0.620

Asia WGS AF: 0.646 AC: 2242 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.39
CADD	Benign	15
DANN	Benign	0.78
PhyloP100		2.2
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: rs12353255; hg19: chr9-20921332;