9-20739883-A-G

Variant names:

• chr9-20739883-A-G
• rs4446809
• NM_001375567.1:c.288-353A>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.288-353A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.806 in 152,088 control chromosomes in the GnomAD database, including 49,699 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 0.81 (49699 hom., cov: 32)
• Consequence: FOCAD NM_001375567.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0700
• Publications: 2 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=-0.66).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.863 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001375567.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOCAD	NM_001375567.1	MANE Select	c.288-353A>G		intron	N/A	NP_001362496.1
	FOCAD	NM_017794.5		c.288-353A>G		intron	N/A	NP_060264.4
	FOCAD	NM_001375568.1		c.288-353A>G		intron	N/A	NP_001362497.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOCAD	ENST00000338382.11	TSL:5 MANE Select	c.288-353A>G		intron	N/A	ENSP00000344307.6
	FOCAD	ENST00000380249.5	TSL:1	c.288-353A>G		intron	N/A	ENSP00000369599.1
	FOCAD	ENST00000604103.1	TSL:4	n.83-353A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.806 AC: 122522 AN: 151970 Hom.: 49669 Cov.: 32

Gnomad AFR AF: 0.716

Gnomad AMI AF: 0.818

Gnomad AMR AF: 0.875

Gnomad ASJ AF: 0.793

Gnomad EAS AF: 0.791

Gnomad SAS AF: 0.845

Gnomad FIN AF: 0.883

Gnomad MID AF: 0.823

Gnomad NFE AF: 0.832

Gnomad OTH AF: 0.827

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

GnomAD4 genome AF: 0.806 AC: 122601 AN: 152088 Hom.: 49699 Cov.: 32 AF XY: 0.809 AC XY: 60130 AN XY: 74342

African (AFR) AF: 0.716 AC: 29690 AN: 41476

American (AMR) AF: 0.876 AC: 13369 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.793 AC: 2748 AN: 3466

East Asian (EAS) AF: 0.791 AC: 4099 AN: 5182

South Asian (SAS) AF: 0.847 AC: 4084 AN: 4824

European-Finnish (FIN) AF: 0.883 AC: 9333 AN: 10574

Middle Eastern (MID) AF: 0.830 AC: 244 AN: 294

European-Non Finnish (NFE) AF: 0.832 AC: 56553 AN: 67980

Other (OTH) AF: 0.821 AC: 1735 AN: 2112

Alfa AF: 0.820 Hom.: 22491

Bravo AF: 0.800

Asia WGS AF: 0.780 AC: 2711 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	8.8
DANN	Benign	0.64
PhyloP100		-0.070
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: rs4446809; hg19: chr9-20739882;