rs7875153

Variant names:

• chr9-20778632-A-G
• rs7875153
• NM_001375567.1:c.907-49A>G

Your query was ambiguous. Multiple possible variants found:

• chr9-20778632-A-G
• chr9-20778632-A-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001375567.1(FOCAD):​c.907-49A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.854 in 996,018 control chromosomes in the GnomAD database, including 364,082 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.84 (53699 hom., cov: 32)
  • Exomes 𝑓: 0.86 (310383 hom.)
• Consequence: FOCAD NM_001375567.1 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0820
• Publications: 9 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BP6: Variant 9-20778632-A-G is Benign according to our data. Variant chr9-20778632-A-G is described in ClinVar as Benign. ClinVar VariationId is 1281513.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.886 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FOCAD	NM_001375567.1	c.907-49A>G		intron_variant	Intron 8 of 43	ENST00000338382.11	NP_001362496.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FOCAD	ENST00000338382.11	c.907-49A>G		intron_variant	Intron 8 of 43	5	NM_001375567.1	ENSP00000344307.6
FOCAD	ENST00000380249.5	c.907-49A>G		intron_variant	Intron 10 of 45	1		ENSP00000369599.1

Frequencies

GnomAD3 genomes AF: 0.839 AC: 127618 AN: 152102 Hom.: 53667 Cov.: 32

Gnomad AFR AF: 0.784

Gnomad AMI AF: 0.852

Gnomad AMR AF: 0.898

Gnomad ASJ AF: 0.841

Gnomad EAS AF: 0.773

Gnomad SAS AF: 0.852

Gnomad FIN AF: 0.891

Gnomad MID AF: 0.873

Gnomad NFE AF: 0.855

Gnomad OTH AF: 0.856

GnomAD2 exomes AF: 0.857 AC: 188778 AN: 220250 AF XY: 0.858

Gnomad AFR exome AF: 0.785

Gnomad AMR exome AF: 0.939

Gnomad ASJ exome AF: 0.830

Gnomad EAS exome AF: 0.766

Gnomad FIN exome AF: 0.887

Gnomad NFE exome AF: 0.852

Gnomad OTH exome AF: 0.869

GnomAD4 exome AF: 0.857 AC: 723141 AN: 843796 Hom.: 310383 Cov.: 11 AF XY: 0.857 AC XY: 379572 AN XY: 442704

African (AFR) AF: 0.792 AC: 17337 AN: 21884

American (AMR) AF: 0.934 AC: 38162 AN: 40874

Ashkenazi Jewish (ASJ) AF: 0.838 AC: 18205 AN: 21722

East Asian (EAS) AF: 0.812 AC: 29799 AN: 36712

South Asian (SAS) AF: 0.861 AC: 60890 AN: 70754

European-Finnish (FIN) AF: 0.886 AC: 44785 AN: 50558

Middle Eastern (MID) AF: 0.896 AC: 4063 AN: 4534

European-Non Finnish (NFE) AF: 0.854 AC: 476017 AN: 557072

Other (OTH) AF: 0.854 AC: 33883 AN: 39686

GnomAD4 genome AF: 0.839 AC: 127699 AN: 152222 Hom.: 53699 Cov.: 32 AF XY: 0.841 AC XY: 62621 AN XY: 74440

African (AFR) AF: 0.783 AC: 32503 AN: 41496

American (AMR) AF: 0.898 AC: 13739 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.841 AC: 2917 AN: 3470

East Asian (EAS) AF: 0.773 AC: 4014 AN: 5192

South Asian (SAS) AF: 0.852 AC: 4119 AN: 4832

European-Finnish (FIN) AF: 0.891 AC: 9443 AN: 10604

Middle Eastern (MID) AF: 0.881 AC: 259 AN: 294

European-Non Finnish (NFE) AF: 0.855 AC: 58132 AN: 68012

Other (OTH) AF: 0.850 AC: 1796 AN: 2114

Alfa AF: 0.843 Hom.: 11109

Bravo AF: 0.835

Asia WGS AF: 0.783 AC: 2724 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 14, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	5.4
DANN	Benign	0.89
PhyloP100		0.082
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: rs7875153; hg19: chr9-20778631; COSMIC: COSV58099130;