NM_001375567.1:c.-33+3825G>A

Variant names:

• chr9-20688118-G-A
• rs12336110
• NM_001375567.1:c.-33+3825G>A

Variant summary

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

The NM_001375567.1(FOCAD):​c.-33+3825G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.204 in 152,128 control chromosomes in the GnomAD database, including 3,373 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 0.20 (3373 hom., cov: 32)
• Consequence: FOCAD NM_001375567.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.688
• Publications: 5 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.272 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FOCAD	NM_001375567.1	c.-33+3825G>A		intron_variant	Intron 1 of 43	ENST00000338382.11	NP_001362496.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FOCAD	ENST00000338382.11	c.-33+3825G>A		intron_variant	Intron 1 of 43	5	NM_001375567.1	ENSP00000344307.6
FOCAD	ENST00000380249.5	c.-77-6402G>A		intron_variant	Intron 2 of 45	1		ENSP00000369599.1

Frequencies

GnomAD3 genomes AF: 0.204 AC: 30991 AN: 152010 Hom.: 3352 Cov.: 32

Gnomad AFR AF: 0.276

Gnomad AMI AF: 0.297

Gnomad AMR AF: 0.165

Gnomad ASJ AF: 0.157

Gnomad EAS AF: 0.162

Gnomad SAS AF: 0.129

Gnomad FIN AF: 0.160

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.186

Gnomad OTH AF: 0.189

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

GnomAD4 genome AF: 0.204 AC: 31049 AN: 152128 Hom.: 3373 Cov.: 32 AF XY: 0.201 AC XY: 14954 AN XY: 74382

African (AFR) AF: 0.276 AC: 11451 AN: 41486

American (AMR) AF: 0.165 AC: 2528 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.157 AC: 543 AN: 3468

East Asian (EAS) AF: 0.162 AC: 842 AN: 5182

South Asian (SAS) AF: 0.131 AC: 630 AN: 4824

European-Finnish (FIN) AF: 0.160 AC: 1688 AN: 10580

Middle Eastern (MID) AF: 0.167 AC: 49 AN: 294

European-Non Finnish (NFE) AF: 0.186 AC: 12656 AN: 67988

Other (OTH) AF: 0.186 AC: 392 AN: 2104

Alfa AF: 0.195 Hom.: 788

Bravo AF: 0.207

Asia WGS AF: 0.158 AC: 546 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.44
DANN	Benign	0.34
PhyloP100		-0.69
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: rs12336110; hg19: chr9-20688117;