rs2298141

Variant names:

• chr10-32925874-A-G
• rs2298141
• NM_002211.4:c.783T>C

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.783T>C​(p.Cys261Cys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.16 in 1,592,456 control chromosomes in the GnomAD database, including 21,627 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 0.14 (1750 hom., cov: 32)
  • Exomes 𝑓: 0.16 (19877 hom.)
• Consequence: ITGB1 NM_002211.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.24
• Publications: 30 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=-0.54).
• BP7: Synonymous conserved (PhyloP=3.24 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.237 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITGB1	NM_002211.4	c.783T>C	p.Cys261Cys	synonymous_variant	Exon 6 of 16	ENST00000302278.8	NP_002202.2
ITGB1	NM_033668.2	c.783T>C	p.Cys261Cys	synonymous_variant	Exon 5 of 16		NP_391988.1
ITGB1	NM_133376.3	c.783T>C	p.Cys261Cys	synonymous_variant	Exon 6 of 16		NP_596867.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITGB1	ENST00000302278.8	c.783T>C	p.Cys261Cys	synonymous_variant	Exon 6 of 16	1	NM_002211.4	ENSP00000303351.3

Frequencies

GnomAD3 genomes AF: 0.140 AC: 21251 AN: 152140 Hom.: 1752 Cov.: 32

Gnomad AFR AF: 0.0552

Gnomad AMI AF: 0.180

Gnomad AMR AF: 0.185

Gnomad ASJ AF: 0.200

Gnomad EAS AF: 0.248

Gnomad SAS AF: 0.167

Gnomad FIN AF: 0.152

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.164

Gnomad OTH AF: 0.168

GnomAD2 exomes AF: 0.168 AC: 42086 AN: 250904 AF XY: 0.168

Gnomad AFR exome AF: 0.0538

Gnomad AMR exome AF: 0.188

Gnomad ASJ exome AF: 0.202

Gnomad EAS exome AF: 0.250

Gnomad FIN exome AF: 0.145

Gnomad NFE exome AF: 0.165

Gnomad OTH exome AF: 0.186

GnomAD4 exome AF: 0.163 AC: 234134 AN: 1440198 Hom.: 19877 Cov.: 28 AF XY: 0.163 AC XY: 116955 AN XY: 717706

African (AFR) AF: 0.0479 AC: 1586 AN: 33112

American (AMR) AF: 0.190 AC: 8502 AN: 44692

Ashkenazi Jewish (ASJ) AF: 0.198 AC: 5130 AN: 25960

East Asian (EAS) AF: 0.250 AC: 9877 AN: 39586

South Asian (SAS) AF: 0.163 AC: 13976 AN: 85798

European-Finnish (FIN) AF: 0.144 AC: 7701 AN: 53394

Middle Eastern (MID) AF: 0.194 AC: 1107 AN: 5716

European-Non Finnish (NFE) AF: 0.161 AC: 175923 AN: 1092288

Other (OTH) AF: 0.173 AC: 10332 AN: 59652

GnomAD4 genome AF: 0.140 AC: 21259 AN: 152258 Hom.: 1750 Cov.: 32 AF XY: 0.140 AC XY: 10440 AN XY: 74434

African (AFR) AF: 0.0552 AC: 2293 AN: 41572

American (AMR) AF: 0.185 AC: 2827 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.200 AC: 693 AN: 3468

East Asian (EAS) AF: 0.248 AC: 1287 AN: 5182

South Asian (SAS) AF: 0.167 AC: 806 AN: 4824

European-Finnish (FIN) AF: 0.152 AC: 1611 AN: 10588

Middle Eastern (MID) AF: 0.194 AC: 57 AN: 294

European-Non Finnish (NFE) AF: 0.164 AC: 11163 AN: 68002

Other (OTH) AF: 0.169 AC: 358 AN: 2116

Alfa AF: 0.163 Hom.: 3552

Bravo AF: 0.139

Asia WGS AF: 0.206 AC: 716 AN: 3478

EpiCase AF: 0.171

EpiControl AF: 0.177

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	9.4
DANN	Benign	0.65
PhyloP100		3.2
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: rs2298141; hg19: chr10-33214802; COSMIC: COSV56479655; COSMIC: COSV56479655;