rs7875153

Positions:

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

Variant summary

Our verdict is Benign. Variant got -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

Genes affected

FOCAD (HGNC:23377): (focadhesin) Located in focal adhesion. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -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 id 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/exons	MANE	Protein	UniProt
FOCAD	NM_001375567.1	c.907-49A>G		intron_variant		ENST00000338382.11	NP_001362496.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FOCAD	ENST00000338382.11	c.907-49A>G		intron_variant		5	NM_001375567.1	ENSP00000344307	P1
FOCAD	ENST00000380249.5	c.907-49A>G		intron_variant		1		ENSP00000369599	P1

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

GnomAD3 exomes AF: 0.857 AC: 188778 AN: 220250 Hom.: 81225 AF XY: 0.858 AC XY: 101764 AN XY: 118652

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 SAS exome AF: 0.861

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

Gnomad4 AFR exome AF: 0.792

Gnomad4 AMR exome AF: 0.934

Gnomad4 ASJ exome AF: 0.838

Gnomad4 EAS exome AF: 0.812

Gnomad4 SAS exome AF: 0.861

Gnomad4 FIN exome AF: 0.886

Gnomad4 NFE exome AF: 0.854

Gnomad4 OTH exome AF: 0.854

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

Gnomad4 AFR AF: 0.783

Gnomad4 AMR AF: 0.898

Gnomad4 ASJ AF: 0.841

Gnomad4 EAS AF: 0.773

Gnomad4 SAS AF: 0.852

Gnomad4 FIN AF: 0.891

Gnomad4 NFE AF: 0.855

Gnomad4 OTH AF: 0.850

Alfa AF: 0.845 Hom.: 10892

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

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 14, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	5.4
DANN	Benign	0.89

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

Publications

LitVar

Other links and lift over

dbSNP: rs7875153; hg19: chr9-20778631; COSMIC: COSV58099130;