17-50056099-G-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000505306.5(ITGA3):n.32G>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.243 in 246,518 control chromosomes in the GnomAD database, including 8,837 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.27 (6467 hom., cov: 32)
  • Exomes 𝑓: 0.20 (2370 hom.)
• Consequence: ITGA3 ENST00000505306.5 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0100

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=-0.79).
• BP6: Variant 17-50056099-G-C is Benign according to our data. Variant chr17-50056099-G-C is described in ClinVar as [Benign]. Clinvar id is 1253387.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.399 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ITGA3	NM_002204.4			upstream_gene_variant		ENST00000320031.13
ITGA3	XM_005257308.3			upstream_gene_variant
ITGA3	XM_047435922.1			upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ITGA3	ENST00000505306.5	n.32G>C		non_coding_transcript_exon_variant	1/24	2
ITGA3	ENST00000506401.6	c.-3+83G>C		intron_variant, NMD_transcript_variant		2
ITGA3	ENST00000320031.13			upstream_gene_variant		1	NM_002204.4	P1

Frequencies

GnomAD3 genomes AF: 0.270 AC: 41057 AN: 151902 Hom.: 6449 Cov.: 32

Gnomad AFR AF: 0.389

Gnomad AMI AF: 0.207

Gnomad AMR AF: 0.378

Gnomad ASJ AF: 0.181

Gnomad EAS AF: 0.413

Gnomad SAS AF: 0.312

Gnomad FIN AF: 0.169

Gnomad MID AF: 0.194

Gnomad NFE AF: 0.182

Gnomad OTH AF: 0.249

GnomAD4 exome AF: 0.198 AC: 18716 AN: 94502 Hom.: 2370 Cov.: 0 AF XY: 0.199 AC XY: 9437 AN XY: 47514

Gnomad4 AFR exome AF: 0.364

Gnomad4 AMR exome AF: 0.403

Gnomad4 ASJ exome AF: 0.176

Gnomad4 EAS exome AF: 0.376

Gnomad4 SAS exome AF: 0.259

Gnomad4 FIN exome AF: 0.148

Gnomad4 NFE exome AF: 0.168

Gnomad4 OTH exome AF: 0.206

GnomAD4 genome AF: 0.271 AC: 41133 AN: 152016 Hom.: 6467 Cov.: 32 AF XY: 0.274 AC XY: 20337 AN XY: 74304

Gnomad4 AFR AF: 0.390

Gnomad4 AMR AF: 0.379

Gnomad4 ASJ AF: 0.181

Gnomad4 EAS AF: 0.414

Gnomad4 SAS AF: 0.310

Gnomad4 FIN AF: 0.169

Gnomad4 NFE AF: 0.182

Gnomad4 OTH AF: 0.253

Alfa AF: 0.0993 Hom.: 124

Bravo AF: 0.293

Asia WGS AF: 0.364 AC: 1267 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
Cadd	Benign	7.5
Dann	Benign	0.38

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs16970080; hg19: chr17-48133463;