rs2291087

Positions:

• chr3-124796651-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002213.5(ITGB5):​c.1430A>G​(p.Asn477Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0369 in 1,613,950 control chromosomes in the GnomAD database, including 1,516 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.048 (254 hom., cov: 33)
  • Exomes 𝑓: 0.036 (1262 hom.)
• Consequence: ITGB5 NM_002213.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.37

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0037605464).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0827 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ITGB5	NM_002213.5	c.1430A>G	p.Asn477Ser	missense_variant	10/15	ENST00000296181.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ITGB5	ENST00000296181.9	c.1430A>G	p.Asn477Ser	missense_variant	10/15	1	NM_002213.5	P1

Frequencies

GnomAD3 genomes AF: 0.0481 AC: 7325 AN: 152164 Hom.: 252 Cov.: 33

Gnomad AFR AF: 0.0848

Gnomad AMI AF: 0.0121

Gnomad AMR AF: 0.0434

Gnomad ASJ AF: 0.0335

Gnomad EAS AF: 0.0328

Gnomad SAS AF: 0.0892

Gnomad FIN AF: 0.0234

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0307

Gnomad OTH AF: 0.0392

GnomAD3 exomes AF: 0.0436 AC: 10911 AN: 250414 Hom.: 342 AF XY: 0.0452 AC XY: 6121 AN XY: 135556

Gnomad AFR exome AF: 0.0887

Gnomad AMR exome AF: 0.0487

Gnomad ASJ exome AF: 0.0280

Gnomad EAS exome AF: 0.0324

Gnomad SAS exome AF: 0.0940

Gnomad FIN exome AF: 0.0230

Gnomad NFE exome AF: 0.0295

Gnomad OTH exome AF: 0.0350

GnomAD4 exome AF: 0.0358 AC: 52289 AN: 1461668 Hom.: 1262 Cov.: 35 AF XY: 0.0371 AC XY: 26999 AN XY: 727148

Gnomad4 AFR exome AF: 0.0885

Gnomad4 AMR exome AF: 0.0499

Gnomad4 ASJ exome AF: 0.0283

Gnomad4 EAS exome AF: 0.0419

Gnomad4 SAS exome AF: 0.0918

Gnomad4 FIN exome AF: 0.0232

Gnomad4 NFE exome AF: 0.0297

Gnomad4 OTH exome AF: 0.0385

GnomAD4 genome AF: 0.0482 AC: 7345 AN: 152282 Hom.: 254 Cov.: 33 AF XY: 0.0478 AC XY: 3562 AN XY: 74456

Gnomad4 AFR AF: 0.0848

Gnomad4 AMR AF: 0.0439

Gnomad4 ASJ AF: 0.0335

Gnomad4 EAS AF: 0.0329

Gnomad4 SAS AF: 0.0897

Gnomad4 FIN AF: 0.0234

Gnomad4 NFE AF: 0.0307

Gnomad4 OTH AF: 0.0393

Alfa AF: 0.0349 Hom.: 168

Bravo AF: 0.0490

TwinsUK AF: 0.0356 AC: 132

ALSPAC AF: 0.0332 AC: 128

ESP6500AA AF: 0.0878 AC: 387

ESP6500EA AF: 0.0302 AC: 260

ExAC AF: 0.0453 AC: 5504

Asia WGS AF: 0.0510 AC: 179 AN: 3478

EpiCase AF: 0.0287

EpiControl AF: 0.0285

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.051
BayesDel_addAF	Benign	-0.52	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	5.7
DANN	Benign	0.18
DEOGEN2	Benign	0.20	T;T
Eigen	Benign	-0.64
Eigen_PC	Benign	-0.59
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.16	T;T
MetaRNN	Benign	0.0038	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-1.1	N;.
MutationTaster	Benign	1.0	P
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-0.56	N;.
REVEL	Benign	0.28
Sift	Benign	0.77	T;.
Sift4G	Benign	0.65	T;.
Polyphen		0.0	B;.
Vest4		0.048
MPC		0.18
ClinPred		0.00073	T
GERP RS		3.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.024
gMVP		0.28

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: rs2291087; hg19: chr3-124515498; COSMIC: COSV56150722; COSMIC: COSV56150722;