10-32922299-T-G

Variant names:

• chr10-32922299-T-G
• rs2230395
• NM_002211.4:c.1086A>C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_002211.4(ITGB1):​c.1086A>C​(p.Ala362Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.118 in 1,606,732 control chromosomes in the GnomAD database, including 13,025 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 0.15 (2021 hom., cov: 32)
  • Exomes 𝑓: 0.11 (11004 hom.)
• Consequence: ITGB1 NM_002211.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.175

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.49).
• BP7: Synonymous conserved (PhyloP=0.175 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.314 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITGB1	NM_002211.4	c.1086A>C	p.Ala362Ala	synonymous_variant	Exon 9 of 16	ENST00000302278.8	NP_002202.2
ITGB1	NM_033668.2	c.1086A>C	p.Ala362Ala	synonymous_variant	Exon 8 of 16		NP_391988.1
ITGB1	NM_133376.3	c.1086A>C	p.Ala362Ala	synonymous_variant	Exon 9 of 16		NP_596867.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITGB1	ENST00000302278.8	c.1086A>C	p.Ala362Ala	synonymous_variant	Exon 9 of 16	1	NM_002211.4	ENSP00000303351.3

Frequencies

GnomAD3 genomes AF: 0.149 AC: 22685 AN: 152026 Hom.: 2023 Cov.: 32

Gnomad AFR AF: 0.234

Gnomad AMI AF: 0.0418

Gnomad AMR AF: 0.111

Gnomad ASJ AF: 0.0916

Gnomad EAS AF: 0.328

Gnomad SAS AF: 0.136

Gnomad FIN AF: 0.122

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.103

Gnomad OTH AF: 0.138

GnomAD3 exomes AF: 0.130 AC: 32133 AN: 247182 Hom.: 2648 AF XY: 0.129 AC XY: 17284 AN XY: 133666

Gnomad AFR exome AF: 0.234

Gnomad AMR exome AF: 0.0817

Gnomad ASJ exome AF: 0.0942

Gnomad EAS exome AF: 0.319

Gnomad SAS exome AF: 0.125

Gnomad FIN exome AF: 0.124

Gnomad NFE exome AF: 0.105

Gnomad OTH exome AF: 0.120

GnomAD4 exome AF: 0.115 AC: 167104 AN: 1454588 Hom.: 11004 Cov.: 29 AF XY: 0.115 AC XY: 83551 AN XY: 723912

Gnomad4 AFR exome AF: 0.239

Gnomad4 AMR exome AF: 0.0855

Gnomad4 ASJ exome AF: 0.0935

Gnomad4 EAS exome AF: 0.310

Gnomad4 SAS exome AF: 0.127

Gnomad4 FIN exome AF: 0.125

Gnomad4 NFE exome AF: 0.104

Gnomad4 OTH exome AF: 0.123

GnomAD4 genome AF: 0.149 AC: 22687 AN: 152144 Hom.: 2021 Cov.: 32 AF XY: 0.151 AC XY: 11210 AN XY: 74372

Gnomad4 AFR AF: 0.234

Gnomad4 AMR AF: 0.111

Gnomad4 ASJ AF: 0.0916

Gnomad4 EAS AF: 0.327

Gnomad4 SAS AF: 0.135

Gnomad4 FIN AF: 0.122

Gnomad4 NFE AF: 0.103

Gnomad4 OTH AF: 0.136

Alfa AF: 0.113 Hom.: 953

Bravo AF: 0.153

Asia WGS AF: 0.177 AC: 615 AN: 3474

EpiCase AF: 0.105

EpiControl AF: 0.105

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
CADD	Benign	8.9
DANN	Benign	0.83

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: rs2230395; hg19: chr10-33211227; COSMIC: COSV56479974; COSMIC: COSV56479974;