17-50089616-C-T

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 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: Genomics England PanelApp, Orphanet, G2P, ClinGen, Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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.

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.*538C>T		3_prime_UTR	Exon 26 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.*538C>T		3_prime_UTR	Exon 26 of 26	ENSP00000315190.8	P26006-2
	ITGA3	ENST00000514834.1	TSL:1	n.661C>T		non_coding_transcript_exon	Exon 2 of 2
	ITGA3	ENST00000007722.11	TSL:5	c.*351C>T		3_prime_UTR	Exon 25 of 25	ENSP00000007722.7	P26006-1

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

African (AFR) AF: 0.0197 AC: 78 AN: 3962

American (AMR) AF: 0.178 AC: 877 AN: 4940

Ashkenazi Jewish (ASJ) AF: 0.0831 AC: 230 AN: 2768

East Asian (EAS) AF: 0.312 AC: 1852 AN: 5940

South Asian (SAS) AF: 0.194 AC: 1088 AN: 5620

European-Finnish (FIN) AF: 0.0751 AC: 283 AN: 3766

Middle Eastern (MID) AF: 0.0684 AC: 26 AN: 380

European-Non Finnish (NFE) AF: 0.0640 AC: 3213 AN: 50202

Other (OTH) AF: 0.0935 AC: 460 AN: 4920

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

African (AFR) AF: 0.0254 AC: 1056 AN: 41524

American (AMR) AF: 0.188 AC: 2863 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.0939 AC: 326 AN: 3470

East Asian (EAS) AF: 0.323 AC: 1656 AN: 5126

South Asian (SAS) AF: 0.245 AC: 1181 AN: 4812

European-Finnish (FIN) AF: 0.0905 AC: 958 AN: 10588

Middle Eastern (MID) AF: 0.0952 AC: 28 AN: 294

European-Non Finnish (NFE) AF: 0.0765 AC: 5203 AN: 68004

Other (OTH) AF: 0.111 AC: 234 AN: 2110

Alfa AF: 0.0821 Hom.: 851

Bravo AF: 0.0911

Asia WGS AF: 0.276 AC: 958 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	10
DANN	Benign	0.84
PhyloP100		2.2
Mutation Taster		=100/0	polymorphism (auto)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs3744538;

hg19: chr17-48166980;

COSMIC: COSV50323327;

COSMIC: COSV50323327;