rs16948627

Variant names:

• chr17-50063432-C-A
• rs16948627
• NM_002204.4:c.207-645C>A

Your query was ambiguous. Multiple possible variants found:

• chr17-50063432-C-A
• chr17-50063432-C-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002204.4(ITGA3):​c.207-645C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0993 in 152,496 control chromosomes in the GnomAD database, including 1,211 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.099 (1210 hom., cov: 32)
  • Exomes 𝑓: 0.086 (1 hom.)
• Consequence: ITGA3 NM_002204.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0380
• Publications: 3 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: Genomics England PanelApp, Orphanet, G2P, ClinGen, Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.31 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.207-645C>A		intron	N/A	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.207-645C>A		intron	N/A	ENSP00000315190.8	P26006-2
	ITGA3	ENST00000007722.11	TSL:5	c.207-645C>A		intron	N/A	ENSP00000007722.7	P26006-1
	ITGA3	ENST00000876971.1		c.207-645C>A		intron	N/A	ENSP00000547030.1

Frequencies

GnomAD3 genomes AF: 0.0992 AC: 15092 AN: 152100 Hom.: 1204 Cov.: 32

Gnomad AFR AF: 0.0241

Gnomad AMI AF: 0.0822

Gnomad AMR AF: 0.223

Gnomad ASJ AF: 0.106

Gnomad EAS AF: 0.322

Gnomad SAS AF: 0.253

Gnomad FIN AF: 0.0993

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.0887

Gnomad OTH AF: 0.112

GnomAD4 exome AF: 0.0863 AC: 24 AN: 278 Hom.: 1 AF XY: 0.0714 AC XY: 12 AN XY: 168

African (AFR) AF: 0.00 AC: 0 AN: 4

American (AMR) AF: 0.00 AC: 0 AN: 8

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2

East Asian (EAS) AF: 0.500 AC: 1 AN: 2

South Asian (SAS) AF: 0.167 AC: 1 AN: 6

European-Finnish (FIN) AF: 0.250 AC: 1 AN: 4

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2

European-Non Finnish (NFE) AF: 0.0861 AC: 21 AN: 244

Other (OTH) AF: 0.00 AC: 0 AN: 6

GnomAD4 genome AF: 0.0993 AC: 15112 AN: 152218 Hom.: 1210 Cov.: 32 AF XY: 0.107 AC XY: 7961 AN XY: 74426

African (AFR) AF: 0.0240 AC: 999 AN: 41556

American (AMR) AF: 0.224 AC: 3427 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.106 AC: 367 AN: 3468

East Asian (EAS) AF: 0.322 AC: 1665 AN: 5164

South Asian (SAS) AF: 0.251 AC: 1214 AN: 4830

European-Finnish (FIN) AF: 0.0993 AC: 1052 AN: 10598

Middle Eastern (MID) AF: 0.102 AC: 30 AN: 294

European-Non Finnish (NFE) AF: 0.0888 AC: 6036 AN: 68004

Other (OTH) AF: 0.117 AC: 247 AN: 2114

Alfa AF: 0.0446 Hom.: 34

Bravo AF: 0.106

Asia WGS AF: 0.274 AC: 952 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	5.8
DANN	Benign	0.84
PhyloP100		-0.038
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs16948627;

hg19: chr17-48140796;