rs2298141

chr10-32925874-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6 BP7 BA1

The NM_002211.4(ITGB1):c.783T>C(p.Cys261=) 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. Variant has been reported in Lovd as Benign (no stars).

• 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

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

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.54).
• BP6: Variant 10-32925874-A-G is Benign according to our data. Variant chr10-32925874-A-G is described in Lovd as [Benign].
• 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/exons	MANE	UniProt
ITGB1	NM_002211.4	c.783T>C	p.Cys261=	synonymous_variant	6/16	ENST00000302278.8
ITGB1	NM_033668.2	c.783T>C	p.Cys261=	synonymous_variant	5/16
ITGB1	NM_133376.3	c.783T>C	p.Cys261=	synonymous_variant	6/16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ITGB1	ENST00000302278.8	c.783T>C	p.Cys261=	synonymous_variant	6/16	1	NM_002211.4	P4

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

GnomAD3 exomes AF: 0.168 AC: 42086 AN: 250904 Hom.: 3793 AF XY: 0.168 AC XY: 22772 AN XY: 135680

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 SAS exome AF: 0.166

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

Gnomad4 AFR exome AF: 0.0479

Gnomad4 AMR exome AF: 0.190

Gnomad4 ASJ exome AF: 0.198

Gnomad4 EAS exome AF: 0.250

Gnomad4 SAS exome AF: 0.163

Gnomad4 FIN exome AF: 0.144

Gnomad4 NFE exome AF: 0.161

Gnomad4 OTH exome AF: 0.173

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

Gnomad4 AFR AF: 0.0552

Gnomad4 AMR AF: 0.185

Gnomad4 ASJ AF: 0.200

Gnomad4 EAS AF: 0.248

Gnomad4 SAS AF: 0.167

Gnomad4 FIN AF: 0.152

Gnomad4 NFE AF: 0.164

Gnomad4 OTH AF: 0.169

Alfa AF: 0.167 Hom.: 2964

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
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: rs2298141; hg19: chr10-33214802; COSMIC: COSV56479655; COSMIC: COSV56479655;