9-20821288-C-T

Variant names:

• chr9-20821288-C-T
• rs1556475
• NM_001375567.1:c.1793+217C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001375567.1(FOCAD):​c.1793+217C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.851 in 152,026 control chromosomes in the GnomAD database, including 55,136 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.85 (55136 hom., cov: 31)
• Consequence: FOCAD NM_001375567.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.246
• Publications: 4 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BP6: Variant 9-20821288-C-T is Benign according to our data. Variant chr9-20821288-C-T is described in ClinVar as Benign. ClinVar VariationId is 1294440.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.88 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.1793+217C>T		intron	N/A	NP_001362496.1
	FOCAD	NM_017794.5		c.1793+217C>T		intron	N/A	NP_060264.4
	FOCAD	NM_001375568.1		c.1688+217C>T		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.1793+217C>T		intron	N/A	ENSP00000344307.6
	FOCAD	ENST00000380249.5	TSL:1	c.1793+217C>T		intron	N/A	ENSP00000369599.1
	FOCAD	ENST00000605086.5	TSL:1	n.263+217C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.851 AC: 129259 AN: 151910 Hom.: 55088 Cov.: 31

Gnomad AFR AF: 0.873

Gnomad AMI AF: 0.852

Gnomad AMR AF: 0.892

Gnomad ASJ AF: 0.796

Gnomad EAS AF: 0.770

Gnomad SAS AF: 0.826

Gnomad FIN AF: 0.887

Gnomad MID AF: 0.838

Gnomad NFE AF: 0.833

Gnomad OTH AF: 0.858

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

GnomAD4 genome AF: 0.851 AC: 129362 AN: 152026 Hom.: 55136 Cov.: 31 AF XY: 0.853 AC XY: 63342 AN XY: 74282

African (AFR) AF: 0.873 AC: 36220 AN: 41502

American (AMR) AF: 0.892 AC: 13595 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.796 AC: 2761 AN: 3470

East Asian (EAS) AF: 0.770 AC: 3974 AN: 5160

South Asian (SAS) AF: 0.826 AC: 3980 AN: 4816

European-Finnish (FIN) AF: 0.887 AC: 9385 AN: 10578

Middle Eastern (MID) AF: 0.846 AC: 247 AN: 292

European-Non Finnish (NFE) AF: 0.833 AC: 56627 AN: 67950

Other (OTH) AF: 0.852 AC: 1796 AN: 2108

Alfa AF: 0.834 Hom.: 69821

Bravo AF: 0.852

Asia WGS AF: 0.783 AC: 2710 AN: 3460

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	5.3
DANN	Benign	0.61
PhyloP100		0.25
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: rs1556475; hg19: chr9-20821287;