rs2291088

Variant names:

• chr3-124796662-G-A
• rs2291088
• NM_002213.5:c.1419C>T
• ITGB5 p.Ser473Ser

Your query was ambiguous. Multiple possible variants found:

• chr3-124796662-G-A
• chr3-124796662-G-C
• chr3-124796662-G-T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_002213.5(ITGB5):​c.1419C>T​(p.Ser473Ser) 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
• Publications: 17 publications found

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

Our verdict: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.178).
• 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002213.5. 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
	ITGB5	NM_002213.5	MANE Select	c.1419C>T	p.Ser473Ser	synonymous	Exon 10 of 15	NP_002204.2
	ITGB5	NM_001354764.2		c.1095C>T	p.Ser365Ser	synonymous	Exon 10 of 15	NP_001341693.1
	ITGB5	NM_001354765.1		c.1095C>T	p.Ser365Ser	synonymous	Exon 10 of 15	NP_001341694.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITGB5	ENST00000296181.9	TSL:1 MANE Select	c.1419C>T	p.Ser473Ser	synonymous	Exon 10 of 15	ENSP00000296181.4	P18084
	ITGB5	ENST00000905025.1		c.1641C>T	p.Ser547Ser	synonymous	Exon 12 of 17	ENSP00000575084.1
	ITGB5	ENST00000965613.1		c.1533C>T	p.Ser511Ser	synonymous	Exon 12 of 17	ENSP00000635672.1

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

GnomAD2 exomes AF: 0.182 AC: 45416 AN: 250072 AF XY: 0.176

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 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

African (AFR) AF: 0.123 AC: 4118 AN: 33480

American (AMR) AF: 0.303 AC: 13548 AN: 44666

Ashkenazi Jewish (ASJ) AF: 0.0802 AC: 2095 AN: 26120

East Asian (EAS) AF: 0.207 AC: 8207 AN: 39696

South Asian (SAS) AF: 0.161 AC: 13922 AN: 86236

European-Finnish (FIN) AF: 0.209 AC: 11137 AN: 53356

Middle Eastern (MID) AF: 0.133 AC: 765 AN: 5742

European-Non Finnish (NFE) AF: 0.166 AC: 184086 AN: 1111924

Other (OTH) AF: 0.160 AC: 9629 AN: 60370

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

African (AFR) AF: 0.127 AC: 5270 AN: 41542

American (AMR) AF: 0.249 AC: 3805 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0744 AC: 258 AN: 3470

East Asian (EAS) AF: 0.174 AC: 896 AN: 5156

South Asian (SAS) AF: 0.158 AC: 763 AN: 4826

European-Finnish (FIN) AF: 0.218 AC: 2306 AN: 10564

Middle Eastern (MID) AF: 0.0918 AC: 27 AN: 294

European-Non Finnish (NFE) AF: 0.162 AC: 11000 AN: 68010

Other (OTH) AF: 0.162 AC: 341 AN: 2110

Alfa AF: 0.148 Hom.: 2516

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	0.78
DANN	Benign	0.45
PhyloP100		2.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=96/4	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: rs2291088;

hg19: chr3-124515509;

COSMIC: COSV56150930;

COSMIC: COSV56150930;