rs73330528

Variant names:

• chr17-50056292-G-A
• rs73330528
• NM_002204.4:c.-148G>A

Your query was ambiguous. Multiple possible variants found:

• chr17-50056292-G-A
• chr17-50056292-G-C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 publications found

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 Gene-Disease associations (from GenCC):

• epidermolysis bullosa, junctional 7, with interstitial lung disease and nephrotic syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics, Genomics England PanelApp, ClinGen

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 48 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002204.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITGA3	NM_002204.4	MANE Select	c.-148G>A		5_prime_UTR	Exon 1 of 26	NP_002195.1	P26006-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITGA3	ENST00000320031.13	TSL:1 MANE Select	c.-148G>A		5_prime_UTR	Exon 1 of 26	ENSP00000315190.8	P26006-2
	ITGA3	ENST00000876973.1		c.-148G>A		5_prime_UTR	Exon 1 of 26	ENSP00000547032.1
	ITGA3	ENST00000876972.1		c.-148G>A		5_prime_UTR	Exon 1 of 26	ENSP00000547031.1

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

African (AFR) AF: 0.0450 AC: 351 AN: 7800

American (AMR) AF: 0.00550 AC: 44 AN: 8004

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 11060

East Asian (EAS) AF: 0.000470 AC: 11 AN: 23420

South Asian (SAS) AF: 0.0000332 AC: 1 AN: 30142

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 28506

Middle Eastern (MID) AF: 0.00233 AC: 4 AN: 1716

European-Non Finnish (NFE) AF: 0.000119 AC: 29 AN: 243096

Other (OTH) AF: 0.00446 AC: 99 AN: 22182

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

African (AFR) AF: 0.0479 AC: 1992 AN: 41578

American (AMR) AF: 0.00562 AC: 86 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.000118 AC: 8 AN: 68024

Other (OTH) AF: 0.00662 AC: 14 AN: 2116

Alfa AF: 0.00342 Hom.: 1

Bravo AF: 0.0155

Asia WGS AF: 0.00202 AC: 8 AN: 3472

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	13
DANN	Benign	0.95
PhyloP100		1.0
PromoterAI		0.019	Neutral
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs73330528; hg19: chr17-48133656;