chr3-124796662-G-A

Position:

• chr3-124796662-G-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_002213.5(ITGB5):​c.1419C>T​(p.Ser473=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.169 in 1,613,754 control chromosomes in the GnomAD database, including 24,068 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 0.16 (2254 hom., cov: 33)
  • Exomes 𝑓: 0.17 (21814 hom.)
• Consequence: ITGB5 NM_002213.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.03

Genes affected

ITGB5 (HGNC:6160): (integrin subunit beta 5) This gene encodes a beta subunit of integrin, which can combine with different alpha chains to form a variety of integrin heterodimers. Integrins are integral cell-surface receptors that participate in cell adhesion as well as cell-surface mediated signaling. The alphav beta5 integrin is involved in adhesion to vitronectin. [provided by RefSeq, Aug 2017]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BP7: Synonymous conserved (PhyloP=2.03 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.242 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ITGB5	NM_002213.5	c.1419C>T	p.Ser473=	synonymous_variant	10/15	ENST00000296181.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ITGB5	ENST00000296181.9	c.1419C>T	p.Ser473=	synonymous_variant	10/15	1	NM_002213.5	P1

Frequencies

GnomAD3 genomes AF: 0.163 AC: 24773 AN: 152046 Hom.: 2253 Cov.: 33

Gnomad AFR AF: 0.127

Gnomad AMI AF: 0.131

Gnomad AMR AF: 0.249

Gnomad ASJ AF: 0.0744

Gnomad EAS AF: 0.173

Gnomad SAS AF: 0.159

Gnomad FIN AF: 0.218

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.162

Gnomad OTH AF: 0.159

GnomAD3 exomes AF: 0.182 AC: 45416 AN: 250072 Hom.: 4721 AF XY: 0.176 AC XY: 23840 AN XY: 135350

Gnomad AFR exome AF: 0.123

Gnomad AMR exome AF: 0.310

Gnomad ASJ exome AF: 0.0785

Gnomad EAS exome AF: 0.175

Gnomad SAS exome AF: 0.161

Gnomad FIN exome AF: 0.217

Gnomad NFE exome AF: 0.160

Gnomad OTH exome AF: 0.168

GnomAD4 exome AF: 0.169 AC: 247507 AN: 1461590 Hom.: 21814 Cov.: 36 AF XY: 0.168 AC XY: 122113 AN XY: 727090

Gnomad4 AFR exome AF: 0.123

Gnomad4 AMR exome AF: 0.303

Gnomad4 ASJ exome AF: 0.0802

Gnomad4 EAS exome AF: 0.207

Gnomad4 SAS exome AF: 0.161

Gnomad4 FIN exome AF: 0.209

Gnomad4 NFE exome AF: 0.166

Gnomad4 OTH exome AF: 0.160

GnomAD4 genome AF: 0.163 AC: 24785 AN: 152164 Hom.: 2254 Cov.: 33 AF XY: 0.167 AC XY: 12385 AN XY: 74376

Gnomad4 AFR AF: 0.127

Gnomad4 AMR AF: 0.249

Gnomad4 ASJ AF: 0.0744

Gnomad4 EAS AF: 0.174

Gnomad4 SAS AF: 0.158

Gnomad4 FIN AF: 0.218

Gnomad4 NFE AF: 0.162

Gnomad4 OTH AF: 0.162

Alfa AF: 0.147 Hom.: 2270

Bravo AF: 0.163

Asia WGS AF: 0.179 AC: 619 AN: 3478

EpiCase AF: 0.160

EpiControl AF: 0.152

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	0.78
DANN	Benign	0.45
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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

Publications

LitVar

Other links and lift over

dbSNP: rs2291088; hg19: chr3-124515509; COSMIC: COSV56150930; COSMIC: COSV56150930;