chr17-50056583-G-C

Variant names:

• chr17-50056583-G-C
• rs1471575304
• NM_002204.4:c.144G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6 BP7

The NM_002204.4(ITGA3):​c.144G>C​(p.Pro48Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000486 in 1,438,878 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000049 (0 hom.)
• Consequence: ITGA3 NM_002204.4 synonymous
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: -0.427
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.4).
• BP6: Variant 17-50056583-G-C is Benign according to our data. Variant chr17-50056583-G-C is described in ClinVar as Likely_benign. ClinVar VariationId is 3055210.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=-0.427 with no splicing effect.

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.144G>C	p.Pro48Pro	synonymous	Exon 1 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.144G>C	p.Pro48Pro	synonymous	Exon 1 of 26	ENSP00000315190.8	P26006-2
	ITGA3	ENST00000007722.11	TSL:5	c.144G>C	p.Pro48Pro	synonymous	Exon 1 of 25	ENSP00000007722.7	P26006-1
	ITGA3	ENST00000876971.1		c.144G>C	p.Pro48Pro	synonymous	Exon 2 of 27	ENSP00000547030.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.0000288 AC: 6 AN: 208244 AF XY: 0.0000176

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000195

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000486 AC: 7 AN: 1438878 Hom.: 0 Cov.: 31 AF XY: 0.00000420 AC XY: 3 AN XY: 713676

African (AFR) AF: 0.00 AC: 0 AN: 32974

American (AMR) AF: 0.000144 AC: 6 AN: 41650

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25718

East Asian (EAS) AF: 0.00 AC: 0 AN: 38410

South Asian (SAS) AF: 0.00 AC: 0 AN: 82762

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50406

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5694

European-Non Finnish (NFE) AF: 9.08e-7 AC: 1 AN: 1101828

Other (OTH) AF: 0.00 AC: 0 AN: 59436

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000936 Hom.: 0

Bravo AF: 0.0000113

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	ITGA3-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.40
CADD	Benign	9.6
DANN	Benign	0.90
PhyloP100		-0.43
PromoterAI		0.022	Neutral

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: rs1471575304; hg19: chr17-48133947;