chr17-50056926-C-T

Position:

• chr17-50056926-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_002204.4(ITGA3):​c.206+281C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00624 in 152,304 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: 𝑓 0.0062 (8 hom., cov: 32)
• Consequence: ITGA3 NM_002204.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.326

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP6: Variant 17-50056926-C-T is Benign according to our data. Variant chr17-50056926-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1223770.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00624 (950/152304) while in subpopulation AFR AF= 0.0216 (899/41548). AF 95% confidence interval is 0.0205. There are 8 homozygotes in gnomad4. There are 421 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ITGA3	NM_002204.4	c.206+281C>T		intron_variant		ENST00000320031.13	NP_002195.1
ITGA3	XM_005257308.3	c.206+281C>T		intron_variant			XP_005257365.1
ITGA3	XM_047435922.1	c.206+281C>T		intron_variant			XP_047291878.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ITGA3	ENST00000320031.13	c.206+281C>T		intron_variant		1	NM_002204.4	ENSP00000315190	P1

Frequencies

GnomAD3 genomes AF: 0.00623 AC: 948 AN: 152186 Hom.: 8 Cov.: 32

Gnomad AFR AF: 0.0217

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00249

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000132

Gnomad OTH AF: 0.00191

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

GnomAD4 genome AF: 0.00624 AC: 950 AN: 152304 Hom.: 8 Cov.: 32 AF XY: 0.00565 AC XY: 421 AN XY: 74482

Gnomad4 AFR AF: 0.0216

Gnomad4 AMR AF: 0.00248

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000132

Gnomad4 OTH AF: 0.00189

Alfa AF: 0.00555 Hom.: 1

Bravo AF: 0.00707

Asia WGS AF: 0.00231 AC: 8 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 31, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	5.9
DANN	Benign	0.78

Splicing

Name	Calibrated prediction	Score	Prediction
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: rs150396898; hg19: chr17-48134290;