chr17-50056292-G-A

Position:

• chr17-50056292-G-A

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.-148G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.005 in 528,244 control chromosomes in the GnomAD database, including 58 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.014 (48 hom., cov: 32)
  • Exomes 𝑓: 0.0014 (10 hom.)
• Consequence: ITGA3 NM_002204.4 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.03

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]

ITGA3 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BP6: Variant 17-50056292-G-A is Benign according to our data. Variant chr17-50056292-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1179289.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0138 (2101/152318) while in subpopulation AFR AF= 0.0479 (1992/41578). AF 95% confidence interval is 0.0462. There are 48 homozygotes in gnomad4. There are 963 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 48 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ITGA3	NM_002204.4	c.-148G>A		5_prime_UTR_variant	1/26	ENST00000320031.13	NP_002195.1
ITGA3	XM_005257308.3	c.-148G>A		5_prime_UTR_variant	1/24		XP_005257365.1
ITGA3	XM_047435922.1	c.-148G>A		5_prime_UTR_variant	1/18		XP_047291878.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ITGA3	ENST00000320031.13	c.-148G>A		5_prime_UTR_variant	1/26	1	NM_002204.4	ENSP00000315190.8
ITGA3	ENST00000505306.5	n.225G>A		non_coding_transcript_exon_variant	1/24	2
ITGA3	ENST00000506401.6	n.-2-146G>A		intron_variant		2		ENSP00000422826.2

Frequencies

GnomAD3 genomes AF: 0.0138 AC: 2097 AN: 152210 Hom.: 48 Cov.: 32

Gnomad AFR AF: 0.0479

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00563

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.00669

GnomAD4 exome AF: 0.00143 AC: 539 AN: 375926 Hom.: 10 Cov.: 5 AF XY: 0.00120 AC XY: 236 AN XY: 196944

Gnomad4 AFR exome AF: 0.0450

Gnomad4 AMR exome AF: 0.00550

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000470

Gnomad4 SAS exome AF: 0.0000332

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000119

Gnomad4 OTH exome AF: 0.00446

GnomAD4 genome AF: 0.0138 AC: 2101 AN: 152318 Hom.: 48 Cov.: 32 AF XY: 0.0129 AC XY: 963 AN XY: 74472

Gnomad4 AFR AF: 0.0479

Gnomad4 AMR AF: 0.00562

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000118

Gnomad4 OTH AF: 0.00662

Alfa AF: 0.00155 Hom.: 1

Bravo AF: 0.0155

Asia WGS AF: 0.00202 AC: 8 AN: 3472

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 26, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	13
DANN	Benign	0.95

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs73330528; hg19: chr17-48133656;