17-50056858-T-A

Position:

• chr17-50056858-T-A

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BS1 BS2

The NM_002204.4(ITGA3):​c.206+213T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00863 in 152,216 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency: Genomes: 𝑓 0.0086 (11 hom., cov: 32)
• Consequence: ITGA3 NM_002204.4 intron
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.892

Genes affected

ITGA3 (HGNC:6139): (integrin subunit alpha 3) The gene encodes a member of the integrin alpha chain family of proteins. Integrins are heterodimeric integral membrane proteins composed of an alpha chain and a beta chain that function as cell surface adhesion molecules. The encoded preproprotein is proteolytically processed to generate light and heavy chains that comprise the alpha 3 subunit. This subunit joins with a beta 1 subunit to form an integrin that interacts with extracellular matrix proteins including members of the laminin family. Expression of this gene may be correlated with breast cancer metastasis. [provided by RefSeq, Oct 2015]

ACMG classification

Verdict is Benign. Variant got -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.42).
• BP6: Variant 17-50056858-T-A is Benign according to our data. Variant chr17-50056858-T-A is described in ClinVar as [Likely_benign]. Clinvar id is 1200358.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00863 (1314/152216) while in subpopulation NFE AF= 0.0128 (873/68004). AF 95% confidence interval is 0.0121. There are 11 homozygotes in gnomad4. There are 627 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 11 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ITGA3	NM_002204.4	c.206+213T>A		intron_variant		ENST00000320031.13	NP_002195.1
ITGA3	XM_005257308.3	c.206+213T>A		intron_variant			XP_005257365.1
ITGA3	XM_047435922.1	c.206+213T>A		intron_variant			XP_047291878.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ITGA3	ENST00000320031.13	c.206+213T>A		intron_variant		1	NM_002204.4	ENSP00000315190	P1

Frequencies

GnomAD3 genomes AF: 0.00864 AC: 1314 AN: 152098 Hom.: 11 Cov.: 32

Gnomad AFR AF: 0.00208

Gnomad AMI AF: 0.0121

Gnomad AMR AF: 0.0100

Gnomad ASJ AF: 0.0133

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00145

Gnomad FIN AF: 0.00980

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0128

Gnomad OTH AF: 0.0134

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

GnomAD4 genome AF: 0.00863 AC: 1314 AN: 152216 Hom.: 11 Cov.: 32 AF XY: 0.00842 AC XY: 627 AN XY: 74450

Gnomad4 AFR AF: 0.00207

Gnomad4 AMR AF: 0.0100

Gnomad4 ASJ AF: 0.0133

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00166

Gnomad4 FIN AF: 0.00980

Gnomad4 NFE AF: 0.0128

Gnomad4 OTH AF: 0.0132

Alfa AF: 0.00783 Hom.: 0

Bravo AF: 0.00821

Asia WGS AF: 0.00202 AC: 7 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 05, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.42
CADD	Benign	18
DANN	Benign	0.92

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: rs140470466; hg19: chr17-48134222;