rs10964759

Variant names:

• chr9-20925922-A-G
• rs10964759
• NM_001375567.1:c.2962-379A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001375567.1(FOCAD):​c.2962-379A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0616 in 152,266 control chromosomes in the GnomAD database, including 475 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 0.062 (475 hom., cov: 32)
• Consequence: FOCAD NM_001375567.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.250
• Publications: 4 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.224 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FOCAD	NM_001375567.1	c.2962-379A>G		intron_variant	Intron 25 of 43	ENST00000338382.11	NP_001362496.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FOCAD	ENST00000338382.11	c.2962-379A>G		intron_variant	Intron 25 of 43	5	NM_001375567.1	ENSP00000344307.6
FOCAD	ENST00000380249.5	c.2962-379A>G		intron_variant	Intron 27 of 45	1		ENSP00000369599.1
FOCAD	ENST00000605086.5	n.1432-379A>G		intron_variant	Intron 13 of 31	1

Frequencies

GnomAD3 genomes AF: 0.0616 AC: 9376 AN: 152148 Hom.: 470 Cov.: 32

Gnomad AFR AF: 0.0153

Gnomad AMI AF: 0.0879

Gnomad AMR AF: 0.0379

Gnomad ASJ AF: 0.0326

Gnomad EAS AF: 0.235

Gnomad SAS AF: 0.127

Gnomad FIN AF: 0.0825

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0758

Gnomad OTH AF: 0.0445

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

GnomAD4 genome AF: 0.0616 AC: 9380 AN: 152266 Hom.: 475 Cov.: 32 AF XY: 0.0636 AC XY: 4736 AN XY: 74462

African (AFR) AF: 0.0153 AC: 636 AN: 41572

American (AMR) AF: 0.0378 AC: 578 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0326 AC: 113 AN: 3464

East Asian (EAS) AF: 0.235 AC: 1214 AN: 5170

South Asian (SAS) AF: 0.126 AC: 608 AN: 4826

European-Finnish (FIN) AF: 0.0825 AC: 876 AN: 10614

Middle Eastern (MID) AF: 0.0442 AC: 13 AN: 294

European-Non Finnish (NFE) AF: 0.0758 AC: 5153 AN: 67996

Other (OTH) AF: 0.0516 AC: 109 AN: 2114

Alfa AF: 0.0675 Hom.: 700

Bravo AF: 0.0558

Asia WGS AF: 0.192 AC: 667 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.72
DANN	Benign	0.80
PhyloP100		-0.25
Mutation Taster		=99/1	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: rs10964759; hg19: chr9-20925921;