rs16948627

chr17-50063432-C-Achr17-50063432-C-T

Variant summary

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

The NM_002204.4(ITGA3):c.207-645C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0993 in 152,496 control chromosomes in the GnomAD database, including 1,211 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 0.099 (1210 hom., cov: 32)
  • Exomes 𝑓: 0.086 (1 hom.)
• Consequence: ITGA3 NM_002204.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0380

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=-0.72).
• 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/exons	MANE	UniProt
ITGA3	NM_002204.4	c.207-645C>A		intron_variant		ENST00000320031.13
ITGA3	XM_005257308.3	c.207-645C>A		intron_variant
ITGA3	XM_047435922.1	c.207-645C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ITGA3	ENST00000320031.13	c.207-645C>A		intron_variant		1	NM_002204.4	P1

Frequencies

GnomAD3 genomes AF: 0.0992 AC: 15092 AN: 152100 Hom.: 1204 Cov.: 32

Gnomad AFR AF: 0.0241

Gnomad AMI AF: 0.0822

Gnomad AMR AF: 0.223

Gnomad ASJ AF: 0.106

Gnomad EAS AF: 0.322

Gnomad SAS AF: 0.253

Gnomad FIN AF: 0.0993

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.0887

Gnomad OTH AF: 0.112

GnomAD4 exome AF: 0.0863 AC: 24 AN: 278 Hom.: 1 AF XY: 0.0714 AC XY: 12 AN XY: 168

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.500

Gnomad4 SAS exome AF: 0.167

Gnomad4 FIN exome AF: 0.250

Gnomad4 NFE exome AF: 0.0861

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0993 AC: 15112 AN: 152218 Hom.: 1210 Cov.: 32 AF XY: 0.107 AC XY: 7961 AN XY: 74426

Gnomad4 AFR AF: 0.0240

Gnomad4 AMR AF: 0.224

Gnomad4 ASJ AF: 0.106

Gnomad4 EAS AF: 0.322

Gnomad4 SAS AF: 0.251

Gnomad4 FIN AF: 0.0993

Gnomad4 NFE AF: 0.0888

Gnomad4 OTH AF: 0.117

Alfa AF: 0.0450 Hom.: 34

Bravo AF: 0.106

Asia WGS AF: 0.274 AC: 952 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
Cadd	Benign	5.8
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: rs16948627; hg19: chr17-48140796;