17-50078061-G-A

Variant names:

• chr17-50078061-G-A
• rs2230392
• NM_002204.4:c.2155G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_002204.4(ITGA3):​c.2155G>A​(p.Ala719Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.103 in 1,610,498 control chromosomes in the GnomAD database, including 11,729 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.095 (1082 hom., cov: 32)
  • Exomes 𝑓: 0.10 (10647 hom.)
• Consequence: ITGA3 NM_002204.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 1.53
• Publications: 29 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0030632317).
• BP6: Variant 17-50078061-G-A is Benign according to our data. Variant chr17-50078061-G-A is described in ClinVar as Benign. ClinVar VariationId is 1237071.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.305 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITGA3	NM_002204.4	MANE Select	c.2155G>A	p.Ala719Thr	missense	Exon 17 of 26	NP_002195.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITGA3	ENST00000320031.13	TSL:1 MANE Select	c.2155G>A	p.Ala719Thr	missense	Exon 17 of 26	ENSP00000315190.8
	ITGA3	ENST00000007722.11	TSL:5	c.2155G>A	p.Ala719Thr	missense	Exon 17 of 25	ENSP00000007722.7
	ITGA3	ENST00000506827.1	TSL:3	c.289G>A	p.Ala97Thr	missense	Exon 4 of 7	ENSP00000426142.1

Frequencies

GnomAD3 genomes AF: 0.0952 AC: 14477 AN: 152042 Hom.: 1080 Cov.: 32

Gnomad AFR AF: 0.0235

Gnomad AMI AF: 0.0822

Gnomad AMR AF: 0.192

Gnomad ASJ AF: 0.105

Gnomad EAS AF: 0.317

Gnomad SAS AF: 0.255

Gnomad FIN AF: 0.0990

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.0874

Gnomad OTH AF: 0.111

GnomAD2 exomes AF: 0.143 AC: 35811 AN: 250822 AF XY: 0.144

Gnomad AFR exome AF: 0.0209

Gnomad AMR exome AF: 0.236

Gnomad ASJ exome AF: 0.0969

Gnomad EAS exome AF: 0.324

Gnomad FIN exome AF: 0.0999

Gnomad NFE exome AF: 0.0911

Gnomad OTH exome AF: 0.130

GnomAD4 exome AF: 0.104 AC: 151264 AN: 1458338 Hom.: 10647 Cov.: 33 AF XY: 0.107 AC XY: 77698 AN XY: 724896

African (AFR) AF: 0.0183 AC: 613 AN: 33444

American (AMR) AF: 0.230 AC: 10259 AN: 44606

Ashkenazi Jewish (ASJ) AF: 0.0998 AC: 2602 AN: 26084

East Asian (EAS) AF: 0.318 AC: 12597 AN: 39586

South Asian (SAS) AF: 0.233 AC: 20011 AN: 85990

European-Finnish (FIN) AF: 0.0981 AC: 5234 AN: 53354

Middle Eastern (MID) AF: 0.106 AC: 610 AN: 5754

European-Non Finnish (NFE) AF: 0.0835 AC: 92660 AN: 1109364

Other (OTH) AF: 0.111 AC: 6678 AN: 60156

GnomAD4 genome AF: 0.0952 AC: 14491 AN: 152160 Hom.: 1082 Cov.: 32 AF XY: 0.103 AC XY: 7652 AN XY: 74390

African (AFR) AF: 0.0235 AC: 975 AN: 41518

American (AMR) AF: 0.193 AC: 2949 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.105 AC: 365 AN: 3472

East Asian (EAS) AF: 0.318 AC: 1636 AN: 5144

South Asian (SAS) AF: 0.253 AC: 1222 AN: 4822

European-Finnish (FIN) AF: 0.0990 AC: 1049 AN: 10594

Middle Eastern (MID) AF: 0.105 AC: 31 AN: 294

European-Non Finnish (NFE) AF: 0.0874 AC: 5944 AN: 68006

Other (OTH) AF: 0.116 AC: 245 AN: 2112

Alfa AF: 0.0982 Hom.: 2449

Bravo AF: 0.0966

TwinsUK AF: 0.0885 AC: 328

ALSPAC AF: 0.0807 AC: 311

ESP6500AA AF: 0.0225 AC: 99

ESP6500EA AF: 0.0888 AC: 764

ExAC AF: 0.138 AC: 16782

Asia WGS AF: 0.275 AC: 955 AN: 3478

EpiCase AF: 0.0914

EpiControl AF: 0.0936

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.087
BayesDel_addAF	Benign	-0.62	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	15
DANN	Uncertain	0.99
DEOGEN2	Benign	0.065	T
Eigen	Benign	-0.076
Eigen_PC	Benign	-0.0095
FATHMM_MKL	Benign	0.48	N
LIST_S2	Benign	0.75	T
MetaRNN	Benign	0.0031	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.4	L
PhyloP100		1.5
PrimateAI	Benign	0.35	T
PROVEAN	Benign	0.27	N
REVEL	Benign	0.010
Sift	Benign	0.36	T
Sift4G	Benign	0.38	T
Polyphen		0.20	B
Vest4		0.026
MPC		0.36
ClinPred		0.0099	T
GERP RS		3.2
Varity_R		0.050
gMVP		0.39
Mutation Taster		=99/1	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: rs2230392; hg19: chr17-48155425; COSMIC: COSV50307095; COSMIC: COSV50307095;