chr17-50073989-T-C

Variant names:

• chr17-50073989-T-C
• rs2285524
• NM_002204.4:c.1230T>C

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_002204.4(ITGA3):​c.1230T>C​(p.Leu410Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.157 in 1,612,682 control chromosomes in the GnomAD database, including 26,897 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.24 (5698 hom., cov: 32)
  • Exomes 𝑓: 0.15 (21199 hom.)
• Consequence: ITGA3 NM_002204.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -1.91
• Publications: 24 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 17-50073989-T-C is Benign according to our data. Variant chr17-50073989-T-C is described in ClinVar as Benign. ClinVar VariationId is 1271172.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.91 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.416 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.1230T>C	p.Leu410Leu	synonymous	Exon 8 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.1230T>C	p.Leu410Leu	synonymous	Exon 8 of 26	ENSP00000315190.8	P26006-2
	ITGA3	ENST00000007722.11	TSL:5	c.1230T>C	p.Leu410Leu	synonymous	Exon 8 of 25	ENSP00000007722.7	P26006-1
	ITGA3	ENST00000876971.1		c.1230T>C	p.Leu410Leu	synonymous	Exon 9 of 27	ENSP00000547030.1

Frequencies

GnomAD3 genomes AF: 0.238 AC: 36133 AN: 151936 Hom.: 5668 Cov.: 32

Gnomad AFR AF: 0.420

Gnomad AMI AF: 0.136

Gnomad AMR AF: 0.317

Gnomad ASJ AF: 0.130

Gnomad EAS AF: 0.343

Gnomad SAS AF: 0.297

Gnomad FIN AF: 0.137

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.121

Gnomad OTH AF: 0.217

GnomAD2 exomes AF: 0.214 AC: 53173 AN: 248882 AF XY: 0.204

Gnomad AFR exome AF: 0.426

Gnomad AMR exome AF: 0.364

Gnomad ASJ exome AF: 0.125

Gnomad EAS exome AF: 0.341

Gnomad FIN exome AF: 0.137

Gnomad NFE exome AF: 0.122

Gnomad OTH exome AF: 0.179

GnomAD4 exome AF: 0.149 AC: 217757 AN: 1460628 Hom.: 21199 Cov.: 31 AF XY: 0.151 AC XY: 109856 AN XY: 726700

African (AFR) AF: 0.427 AC: 14265 AN: 33434

American (AMR) AF: 0.358 AC: 16013 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.127 AC: 3319 AN: 26134

East Asian (EAS) AF: 0.340 AC: 13497 AN: 39682

South Asian (SAS) AF: 0.275 AC: 23713 AN: 86220

European-Finnish (FIN) AF: 0.137 AC: 7306 AN: 53404

Middle Eastern (MID) AF: 0.144 AC: 833 AN: 5766

European-Non Finnish (NFE) AF: 0.116 AC: 128469 AN: 1110936

Other (OTH) AF: 0.171 AC: 10342 AN: 60342

GnomAD4 genome AF: 0.238 AC: 36234 AN: 152054 Hom.: 5698 Cov.: 32 AF XY: 0.243 AC XY: 18035 AN XY: 74344

African (AFR) AF: 0.421 AC: 17453 AN: 41448

American (AMR) AF: 0.317 AC: 4848 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.130 AC: 449 AN: 3464

East Asian (EAS) AF: 0.344 AC: 1770 AN: 5150

South Asian (SAS) AF: 0.295 AC: 1422 AN: 4820

European-Finnish (FIN) AF: 0.137 AC: 1453 AN: 10606

Middle Eastern (MID) AF: 0.133 AC: 39 AN: 294

European-Non Finnish (NFE) AF: 0.121 AC: 8208 AN: 67972

Other (OTH) AF: 0.222 AC: 468 AN: 2106

Alfa AF: 0.168 Hom.: 2320

Bravo AF: 0.257

Asia WGS AF: 0.339 AC: 1178 AN: 3478

EpiCase AF: 0.123

EpiControl AF: 0.124

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.7
DANN	Benign	0.52
PhyloP100		-1.9
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

Other links and lift over

dbSNP: rs2285524; hg19: chr17-48151353; COSMIC: COSV50307030; COSMIC: COSV50307030;