17-50089616-C-T

Variant names:

• chr17-50089616-C-T
• rs3744538
• NM_002204.4:c.*538C>T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002204.4(ITGA3):​c.*538C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0924 in 234,606 control chromosomes in the GnomAD database, including 1,764 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.089 (1006 hom., cov: 31)
  • Exomes 𝑓: 0.098 (758 hom.)
• Consequence: ITGA3 NM_002204.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.20

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.64).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.31 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITGA3	NM_002204.4	c.*538C>T		3_prime_UTR_variant	Exon 26 of 26	ENST00000320031.13	NP_002195.1
ITGA3	XM_005257308.3	c.*538C>T		3_prime_UTR_variant	Exon 24 of 24		XP_005257365.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITGA3	ENST00000320031.13	c.*538C>T		3_prime_UTR_variant	Exon 26 of 26	1	NM_002204.4	ENSP00000315190.8

Frequencies

GnomAD3 genomes AF: 0.0892 AC: 13564 AN: 151990 Hom.: 1004 Cov.: 31

Gnomad AFR AF: 0.0254

Gnomad AMI AF: 0.0822

Gnomad AMR AF: 0.187

Gnomad ASJ AF: 0.0939

Gnomad EAS AF: 0.323

Gnomad SAS AF: 0.247

Gnomad FIN AF: 0.0905

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.0765

Gnomad OTH AF: 0.106

GnomAD4 exome AF: 0.0983 AC: 8107 AN: 82498 Hom.: 758 Cov.: 0 AF XY: 0.102 AC XY: 4319 AN XY: 42542

Gnomad4 AFR exome AF: 0.0197

Gnomad4 AMR exome AF: 0.178

Gnomad4 ASJ exome AF: 0.0831

Gnomad4 EAS exome AF: 0.312

Gnomad4 SAS exome AF: 0.194

Gnomad4 FIN exome AF: 0.0751

Gnomad4 NFE exome AF: 0.0640

Gnomad4 OTH exome AF: 0.0935

GnomAD4 genome AF: 0.0893 AC: 13580 AN: 152108 Hom.: 1006 Cov.: 31 AF XY: 0.0964 AC XY: 7169 AN XY: 74344

Gnomad4 AFR AF: 0.0254

Gnomad4 AMR AF: 0.188

Gnomad4 ASJ AF: 0.0939

Gnomad4 EAS AF: 0.323

Gnomad4 SAS AF: 0.245

Gnomad4 FIN AF: 0.0905

Gnomad4 NFE AF: 0.0765

Gnomad4 OTH AF: 0.111

Alfa AF: 0.0808 Hom.: 625

Bravo AF: 0.0911

Asia WGS AF: 0.276 AC: 958 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	10
DANN	Benign	0.84

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: rs3744538; hg19: chr17-48166980; COSMIC: COSV50323327; COSMIC: COSV50323327;