rs2230394

Variant names:

• chr10-32928182-G-A
• rs2230394
• NM_002211.4:c.459C>T

Your query was ambiguous. Multiple possible variants found:

• chr10-32928182-G-A
• chr10-32928182-G-C
• chr10-32928182-G-T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_002211.4(ITGB1):​c.459C>T​(p.Tyr153Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.126 in 1,336,250 control chromosomes in the GnomAD database, including 12,308 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 (2398 hom., cov: 33)
  • Exomes 𝑓: 0.12 (9910 hom.)
• Consequence: ITGB1 NM_002211.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.32
• Publications: 20 publications found

Genes affected

ITGB1 (HGNC:6153): (integrin subunit beta 1) Integrins are heterodimeric proteins made up of alpha and beta subunits. At least 18 alpha and 8 beta subunits have been described in mammals. Integrin family members are membrane receptors involved in cell adhesion and recognition in a variety of processes including embryogenesis, hemostasis, tissue repair, immune response and metastatic diffusion of tumor cells. This gene encodes a beta subunit. Multiple alternatively spliced transcript variants which encode different protein isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BP7: Synonymous conserved (PhyloP=2.32 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.314 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002211.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITGB1	NM_002211.4	MANE Select	c.459C>T	p.Tyr153Tyr	synonymous	Exon 5 of 16	NP_002202.2
	ITGB1	NM_033668.2		c.459C>T	p.Tyr153Tyr	synonymous	Exon 4 of 16	NP_391988.1
	ITGB1	NM_133376.3		c.459C>T	p.Tyr153Tyr	synonymous	Exon 5 of 16	NP_596867.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITGB1	ENST00000302278.8	TSL:1 MANE Select	c.459C>T	p.Tyr153Tyr	synonymous	Exon 5 of 16	ENSP00000303351.3
	ITGB1	ENST00000488427.2	TSL:1	c.288C>T	p.Tyr96Tyr	synonymous	Exon 5 of 16	ENSP00000417508.2
	ITGB1	ENST00000677310.2		c.459C>T	p.Tyr153Tyr	synonymous	Exon 6 of 18	ENSP00000504508.1

Frequencies

GnomAD3 genomes AF: 0.159 AC: 24216 AN: 152002 Hom.: 2396 Cov.: 33

Gnomad AFR AF: 0.267

Gnomad AMI AF: 0.0417

Gnomad AMR AF: 0.120

Gnomad ASJ AF: 0.0917

Gnomad EAS AF: 0.328

Gnomad SAS AF: 0.132

Gnomad FIN AF: 0.122

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.103

Gnomad OTH AF: 0.152

GnomAD2 exomes AF: 0.134 AC: 33512 AN: 250538 AF XY: 0.132

Gnomad AFR exome AF: 0.265

Gnomad AMR exome AF: 0.0876

Gnomad ASJ exome AF: 0.0947

Gnomad EAS exome AF: 0.321

Gnomad FIN exome AF: 0.125

Gnomad NFE exome AF: 0.107

Gnomad OTH exome AF: 0.125

GnomAD4 exome AF: 0.121 AC: 143738 AN: 1184130 Hom.: 9910 Cov.: 20 AF XY: 0.121 AC XY: 72929 AN XY: 602492

African (AFR) AF: 0.275 AC: 7813 AN: 28408

American (AMR) AF: 0.0916 AC: 4059 AN: 44314

Ashkenazi Jewish (ASJ) AF: 0.0955 AC: 2331 AN: 24416

East Asian (EAS) AF: 0.311 AC: 11956 AN: 38444

South Asian (SAS) AF: 0.127 AC: 10217 AN: 80508

European-Finnish (FIN) AF: 0.125 AC: 6656 AN: 53260

Middle Eastern (MID) AF: 0.147 AC: 770 AN: 5236

European-Non Finnish (NFE) AF: 0.109 AC: 93323 AN: 858374

Other (OTH) AF: 0.129 AC: 6613 AN: 51170

GnomAD4 genome AF: 0.159 AC: 24229 AN: 152120 Hom.: 2398 Cov.: 33 AF XY: 0.161 AC XY: 11942 AN XY: 74360

African (AFR) AF: 0.267 AC: 11067 AN: 41442

American (AMR) AF: 0.119 AC: 1823 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0917 AC: 318 AN: 3468

East Asian (EAS) AF: 0.327 AC: 1692 AN: 5180

South Asian (SAS) AF: 0.131 AC: 634 AN: 4826

European-Finnish (FIN) AF: 0.122 AC: 1293 AN: 10580

Middle Eastern (MID) AF: 0.136 AC: 40 AN: 294

European-Non Finnish (NFE) AF: 0.103 AC: 7007 AN: 68012

Other (OTH) AF: 0.150 AC: 317 AN: 2114

Alfa AF: 0.121 Hom.: 1502

Bravo AF: 0.163

Asia WGS AF: 0.177 AC: 614 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	6.6
DANN	Benign	0.37
PhyloP100		2.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=99/1	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

Other links and lift over

dbSNP: rs2230394; hg19: chr10-33217110; COSMIC: COSV56479684; COSMIC: COSV56479684;