chr9-20715313-T-C

Position:

• chr9-20715313-T-C

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The NM_001375567.1(FOCAD):​c.-32-9T>C variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0593 in 1,380,828 control chromosomes in the GnomAD database, including 2,863 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.055 (243 hom., cov: 32)
  • Exomes 𝑓: 0.060 (2620 hom.)
• Consequence: FOCAD NM_001375567.1 splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.01815
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 3.06

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 -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.25).
• BP6: Variant 9-20715313-T-C is Benign according to our data. Variant chr9-20715313-T-C is described in ClinVar as [Benign]. Clinvar id is 1231527.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0629 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FOCAD	NM_001375567.1	c.-32-9T>C		splice_polypyrimidine_tract_variant, intron_variant		ENST00000338382.11	NP_001362496.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FOCAD	ENST00000338382.11	c.-32-9T>C		splice_polypyrimidine_tract_variant, intron_variant		5	NM_001375567.1	ENSP00000344307	P1
FOCAD	ENST00000380249.5	c.-32-9T>C		splice_polypyrimidine_tract_variant, intron_variant		1		ENSP00000369599	P1

Frequencies

GnomAD3 genomes AF: 0.0549 AC: 8360 AN: 152174 Hom.: 241 Cov.: 32

Gnomad AFR AF: 0.0535

Gnomad AMI AF: 0.113

Gnomad AMR AF: 0.0633

Gnomad ASJ AF: 0.0844

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00932

Gnomad FIN AF: 0.0140

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.0645

Gnomad OTH AF: 0.0742

GnomAD3 exomes AF: 0.0469 AC: 9144 AN: 194836 Hom.: 304 AF XY: 0.0470 AC XY: 5029 AN XY: 107032

Gnomad AFR exome AF: 0.0494

Gnomad AMR exome AF: 0.0517

Gnomad ASJ exome AF: 0.0748

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0141

Gnomad FIN exome AF: 0.0158

Gnomad NFE exome AF: 0.0626

Gnomad OTH exome AF: 0.0688

GnomAD4 exome AF: 0.0598 AC: 73461 AN: 1228536 Hom.: 2620 Cov.: 18 AF XY: 0.0592 AC XY: 35928 AN XY: 606500

Gnomad4 AFR exome AF: 0.0546

Gnomad4 AMR exome AF: 0.0549

Gnomad4 ASJ exome AF: 0.0781

Gnomad4 EAS exome AF: 0.0000291

Gnomad4 SAS exome AF: 0.0128

Gnomad4 FIN exome AF: 0.0172

Gnomad4 NFE exome AF: 0.0662

Gnomad4 OTH exome AF: 0.0610

GnomAD4 genome AF: 0.0550 AC: 8376 AN: 152292 Hom.: 243 Cov.: 32 AF XY: 0.0512 AC XY: 3812 AN XY: 74484

Gnomad4 AFR AF: 0.0536

Gnomad4 AMR AF: 0.0633

Gnomad4 ASJ AF: 0.0844

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00933

Gnomad4 FIN AF: 0.0140

Gnomad4 NFE AF: 0.0645

Gnomad4 OTH AF: 0.0739

Alfa AF: 0.0605 Hom.: 80

Bravo AF: 0.0609

Asia WGS AF: 0.0150 AC: 52 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	clinical testing	GeneDx	Jun 14, 2019	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.25
CADD	Benign	20
DANN	Benign	0.82

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.018
dbscSNV1_RF	Benign	0.14
SpliceAI score (max)		0.010		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: rs56301631; hg19: chr9-20715312;