17-50056003-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Moderate BP6_Moderate BS1 BS2

The ENST00000506401.6(ITGA3):c.-16G>A variant causes a 5 prime UTR, NMD transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0134 in 157,686 control chromosomes in the GnomAD database, including 48 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: 0.0017 (0 hom.)
• Consequence: ITGA3 ENST00000506401.6 5_prime_UTR, NMD_transcript
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.16

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=-0.36).
• BP6: Variant 17-50056003-G-A is Benign according to our data. Variant chr17-50056003-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1219843.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 (2098/152298) while in subpopulation AFR AF= 0.0478 (1989/41570). AF 95% confidence interval is 0.0461. There are 48 homozygotes in gnomad4. There are 962 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 48 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ITGA3	ENST00000506401.6	c.-16G>A		5_prime_UTR_variant, NMD_transcript_variant	1/14	2

Frequencies

GnomAD3 genomes AF: 0.0138 AC: 2094 AN: 152184 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: 0.00167 AC: 9 AN: 5388 Hom.: 0 Cov.: 0 AF XY: 0.00213 AC XY: 6 AN XY: 2814

Gnomad4 AFR exome AF: 0.0320

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00278

GnomAD4 genome AF: 0.0138 AC: 2098 AN: 152298 Hom.: 48 Cov.: 32 AF XY: 0.0129 AC XY: 962 AN XY: 74468

Gnomad4 AFR AF: 0.0478

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: 0.0104 Hom.: 4

Bravo AF: 0.0154

Asia WGS AF: 0.00202 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 26, 2020

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.36
Cadd	Benign	15
Dann	Benign	0.97

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs76105399; hg19: chr17-48133367;