rs7851363

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr9-20758307-T-A
• chr9-20758307-T-C

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.494+116T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.238 in 590,904 control chromosomes in the GnomAD database, including 18,059 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.22 (3862 hom., cov: 31)
  • Exomes 𝑓: 0.25 (14197 hom.)
• Consequence: FOCAD NM_001375567.1 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.363
• Publications: 3 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=-0.87).
• BP6: Variant 9-20758307-T-A is Benign according to our data. Variant chr9-20758307-T-A is described in ClinVar as Benign. ClinVar VariationId is 1288052.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.309 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.494+116T>A		intron	N/A	NP_001362496.1
	FOCAD	NM_017794.5		c.494+116T>A		intron	N/A	NP_060264.4
	FOCAD	NM_001375568.1		c.494+116T>A		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.494+116T>A		intron	N/A	ENSP00000344307.6
	FOCAD	ENST00000380249.5	TSL:1	c.494+116T>A		intron	N/A	ENSP00000369599.1
	FOCAD	ENST00000604103.1	TSL:4	n.289+116T>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.215 AC: 32697 AN: 151910 Hom.: 3859 Cov.: 31

Gnomad AFR AF: 0.143

Gnomad AMI AF: 0.312

Gnomad AMR AF: 0.215

Gnomad ASJ AF: 0.183

Gnomad EAS AF: 0.0483

Gnomad SAS AF: 0.323

Gnomad FIN AF: 0.255

Gnomad MID AF: 0.278

Gnomad NFE AF: 0.258

Gnomad OTH AF: 0.232

GnomAD4 exome AF: 0.246 AC: 107893 AN: 438876 Hom.: 14197 AF XY: 0.251 AC XY: 57774 AN XY: 230452

African (AFR) AF: 0.139 AC: 1504 AN: 10840

American (AMR) AF: 0.209 AC: 2424 AN: 11600

Ashkenazi Jewish (ASJ) AF: 0.175 AC: 2085 AN: 11882

East Asian (EAS) AF: 0.0760 AC: 1992 AN: 26218

South Asian (SAS) AF: 0.318 AC: 9877 AN: 31096

European-Finnish (FIN) AF: 0.252 AC: 7945 AN: 31588

Middle Eastern (MID) AF: 0.288 AC: 823 AN: 2856

European-Non Finnish (NFE) AF: 0.262 AC: 75792 AN: 289494

Other (OTH) AF: 0.234 AC: 5451 AN: 23302

GnomAD4 genome AF: 0.215 AC: 32712 AN: 152028 Hom.: 3862 Cov.: 31 AF XY: 0.214 AC XY: 15924 AN XY: 74310

African (AFR) AF: 0.143 AC: 5957 AN: 41522

American (AMR) AF: 0.216 AC: 3290 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.183 AC: 633 AN: 3464

East Asian (EAS) AF: 0.0484 AC: 251 AN: 5184

South Asian (SAS) AF: 0.323 AC: 1552 AN: 4810

European-Finnish (FIN) AF: 0.255 AC: 2678 AN: 10516

Middle Eastern (MID) AF: 0.276 AC: 81 AN: 294

European-Non Finnish (NFE) AF: 0.258 AC: 17500 AN: 67954

Other (OTH) AF: 0.230 AC: 486 AN: 2114

Alfa AF: 0.230 Hom.: 602

Bravo AF: 0.208

Asia WGS AF: 0.182 AC: 631 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.0
DANN	Benign	0.56
PhyloP100		-0.36
Mutation Taster		=100/0	polymorphism (auto)

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;