rs2230392

chr17-50078061-G-A

Variant summary

Our verdict is Benign. Variant got -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. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• 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:2
• Conservation: PhyloP100: 1.53

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 -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 id is 1237071.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-50078061-G-A is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.305 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ITGA3	NM_002204.4	c.2155G>A	p.Ala719Thr	missense_variant	17/26	ENST00000320031.13
ITGA3	XM_005257308.3	c.1750G>A	p.Ala584Thr	missense_variant	15/24
ITGA3	XM_047435922.1	c.2196G>A	p.Ser732=	synonymous_variant	17/18

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ITGA3	ENST00000320031.13	c.2155G>A	p.Ala719Thr	missense_variant	17/26	1	NM_002204.4	P1

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

GnomAD3 exomes AF: 0.143 AC: 35811 AN: 250822 Hom.: 3574 AF XY: 0.144 AC XY: 19449 AN XY: 135506

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 SAS exome AF: 0.233

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

Gnomad4 AFR exome AF: 0.0183

Gnomad4 AMR exome AF: 0.230

Gnomad4 ASJ exome AF: 0.0998

Gnomad4 EAS exome AF: 0.318

Gnomad4 SAS exome AF: 0.233

Gnomad4 FIN exome AF: 0.0981

Gnomad4 NFE exome AF: 0.0835

Gnomad4 OTH exome AF: 0.111

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

Gnomad4 AFR AF: 0.0235

Gnomad4 AMR AF: 0.193

Gnomad4 ASJ AF: 0.105

Gnomad4 EAS AF: 0.318

Gnomad4 SAS AF: 0.253

Gnomad4 FIN AF: 0.0990

Gnomad4 NFE AF: 0.0874

Gnomad4 OTH AF: 0.116

Alfa AF: 0.0989 Hom.: 1793

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:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -

Computational scores

Source: dbNSFP v4.3

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;T
MetaRNN	Benign	0.0031	T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.4	L;L
MutationTaster	Benign	0.93	P;P
PrimateAI	Benign	0.35	T
PROVEAN	Benign	0.27	N;N
REVEL	Benign	0.010
Sift	Benign	0.36	T;T
Sift4G	Benign	0.38	T;T
Polyphen		0.20	B;B
Vest4		0.026
MPC		0.36
ClinPred		0.0099	T
GERP RS		3.2
Varity_R		0.050
gMVP		0.39

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

Publications

LitVar

Other links and lift over

dbSNP: rs2230392; hg19: chr17-48155425; COSMIC: COSV50307095; COSMIC: COSV50307095;