chr9-20758307-T-C

Variant names:

• chr9-20758307-T-C
• rs7851363
• NM_001375567.1:c.494+116T>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001375567.1(FOCAD):​c.494+116T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000909 in 440,064 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 31)
  • Exomes 𝑓: 0.0000091 (0 hom.)
• Consequence: FOCAD NM_001375567.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.363
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOCAD	NM_001375567.1	MANE Select	c.494+116T>C		intron	N/A	NP_001362496.1	Q5VW36
	FOCAD	NM_017794.5		c.494+116T>C		intron	N/A	NP_060264.4
	FOCAD	NM_001375568.1		c.494+116T>C		intron	N/A	NP_001362497.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOCAD	ENST00000338382.11	TSL:5 MANE Select	c.494+116T>C		intron	N/A	ENSP00000344307.6	Q5VW36
	FOCAD	ENST00000380249.5	TSL:1	c.494+116T>C		intron	N/A	ENSP00000369599.1	Q5VW36
	FOCAD	ENST00000894775.1		c.494+116T>C		intron	N/A	ENSP00000564834.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000909 AC: 4 AN: 440064 Hom.: 0 AF XY: 0.0000130 AC XY: 3 AN XY: 231038

African (AFR) AF: 0.00 AC: 0 AN: 10864

American (AMR) AF: 0.00 AC: 0 AN: 11636

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 11902

East Asian (EAS) AF: 0.00 AC: 0 AN: 26250

South Asian (SAS) AF: 0.00 AC: 0 AN: 31196

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 31662

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2866

European-Non Finnish (NFE) AF: 0.0000138 AC: 4 AN: 290318

Other (OTH) AF: 0.00 AC: 0 AN: 23370

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.8
DANN	Benign	0.70
PhyloP100		-0.36

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs7851363; hg19: chr9-20758306;