rs2269772

Variant names:

• chr17-50072022-C-T
• rs2269772
• NM_002204.4:c.996C>T

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_002204.4(ITGA3):​c.996C>T​(p.Phe332Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.121 in 1,613,448 control chromosomes in the GnomAD database, including 16,649 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.19 (3528 hom., cov: 31)
  • Exomes 𝑓: 0.11 (13121 hom.)
• Consequence: ITGA3 NM_002204.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.999
• Publications: 22 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: PanelApp Australia, Labcorp Genetics (formerly Invitae), Genomics England PanelApp, ClinGen, Ambry Genetics, Orphanet, G2P

ACMG classification

Our verdict: Benign. The variant received -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).
• BP6: Variant 17-50072022-C-T is Benign according to our data. Variant chr17-50072022-C-T is described in ClinVar as Benign. ClinVar VariationId is 1271410.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.999 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.332 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITGA3	NM_002204.4	c.996C>T	p.Phe332Phe	synonymous_variant	Exon 7 of 26	ENST00000320031.13	NP_002195.1
ITGA3	XM_047435922.1	c.996C>T	p.Phe332Phe	synonymous_variant	Exon 7 of 18		XP_047291878.1
ITGA3	XM_005257308.3	c.751+1092C>T		intron_variant	Intron 5 of 23		XP_005257365.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITGA3	ENST00000320031.13	c.996C>T	p.Phe332Phe	synonymous_variant	Exon 7 of 26	1	NM_002204.4	ENSP00000315190.8

Frequencies

GnomAD3 genomes AF: 0.185 AC: 28077 AN: 151844 Hom.: 3511 Cov.: 31

Gnomad AFR AF: 0.336

Gnomad AMI AF: 0.0813

Gnomad AMR AF: 0.224

Gnomad ASJ AF: 0.118

Gnomad EAS AF: 0.315

Gnomad SAS AF: 0.255

Gnomad FIN AF: 0.0975

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.0889

Gnomad OTH AF: 0.165

GnomAD2 exomes AF: 0.167 AC: 41908 AN: 250798 AF XY: 0.162

Gnomad AFR exome AF: 0.344

Gnomad AMR exome AF: 0.250

Gnomad ASJ exome AF: 0.113

Gnomad EAS exome AF: 0.320

Gnomad FIN exome AF: 0.0991

Gnomad NFE exome AF: 0.0927

Gnomad OTH exome AF: 0.141

GnomAD4 exome AF: 0.114 AC: 166596 AN: 1461486 Hom.: 13121 Cov.: 33 AF XY: 0.116 AC XY: 84575 AN XY: 727078

African (AFR) AF: 0.342 AC: 11464 AN: 33476

American (AMR) AF: 0.246 AC: 11012 AN: 44696

Ashkenazi Jewish (ASJ) AF: 0.115 AC: 3002 AN: 26116

East Asian (EAS) AF: 0.316 AC: 12552 AN: 39696

South Asian (SAS) AF: 0.234 AC: 20216 AN: 86242

European-Finnish (FIN) AF: 0.0970 AC: 5179 AN: 53384

Middle Eastern (MID) AF: 0.118 AC: 679 AN: 5760

European-Non Finnish (NFE) AF: 0.0850 AC: 94493 AN: 1111734

Other (OTH) AF: 0.132 AC: 7999 AN: 60382

GnomAD4 genome AF: 0.185 AC: 28157 AN: 151962 Hom.: 3528 Cov.: 31 AF XY: 0.189 AC XY: 14048 AN XY: 74274

African (AFR) AF: 0.337 AC: 13950 AN: 41428

American (AMR) AF: 0.224 AC: 3420 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.118 AC: 410 AN: 3470

East Asian (EAS) AF: 0.316 AC: 1617 AN: 5124

South Asian (SAS) AF: 0.254 AC: 1221 AN: 4816

European-Finnish (FIN) AF: 0.0975 AC: 1032 AN: 10586

Middle Eastern (MID) AF: 0.119 AC: 35 AN: 294

European-Non Finnish (NFE) AF: 0.0889 AC: 6041 AN: 67956

Other (OTH) AF: 0.169 AC: 357 AN: 2110

Alfa AF: 0.125 Hom.: 2715

Bravo AF: 0.199

Asia WGS AF: 0.292 AC: 1016 AN: 3478

EpiCase AF: 0.0936

EpiControl AF: 0.0961

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	8.8
DANN	Benign	0.63
PhyloP100		-1.0
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs2269772; hg19: chr17-48149386; COSMIC: COSV50306944; COSMIC: COSV50306944;