10-32922299-T-G

Variant names:

• chr10-32922299-T-G
• rs2230395
• NM_002211.4:c.1086A>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.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
• Publications: 21 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=-0.49).
• 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

GnomAD2 exomes AF: 0.130 AC: 32133 AN: 247182 AF XY: 0.129

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 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

African (AFR) AF: 0.239 AC: 7920 AN: 33078

American (AMR) AF: 0.0855 AC: 3741 AN: 43742

Ashkenazi Jewish (ASJ) AF: 0.0935 AC: 2436 AN: 26048

East Asian (EAS) AF: 0.310 AC: 12197 AN: 39354

South Asian (SAS) AF: 0.127 AC: 10794 AN: 85314

European-Finnish (FIN) AF: 0.125 AC: 6643 AN: 53156

Middle Eastern (MID) AF: 0.138 AC: 790 AN: 5740

European-Non Finnish (NFE) AF: 0.104 AC: 115191 AN: 1108032

Other (OTH) AF: 0.123 AC: 7392 AN: 60124

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

African (AFR) AF: 0.234 AC: 9702 AN: 41482

American (AMR) AF: 0.111 AC: 1694 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0916 AC: 318 AN: 3472

East Asian (EAS) AF: 0.327 AC: 1687 AN: 5160

South Asian (SAS) AF: 0.135 AC: 653 AN: 4832

European-Finnish (FIN) AF: 0.122 AC: 1287 AN: 10588

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

European-Non Finnish (NFE) AF: 0.103 AC: 6981 AN: 67988

Other (OTH) AF: 0.136 AC: 287 AN: 2116

Alfa AF: 0.120 Hom.: 1779

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
PhyloP100		0.17
Mutation Taster		=98/2	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
Splicevardb		2.0
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: rs2230395; hg19: chr10-33211227; COSMIC: COSV56479974; COSMIC: COSV56479974;