10-32930080-T-G

Variant names:

• chr10-32930080-T-G
• rs2256455
• NM_002211.4:c.154-36A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002211.4(ITGB1):​c.154-36A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.628 in 828,366 control chromosomes in the GnomAD database, including 170,363 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 0.54 (24930 hom., cov: 32)
  • Exomes 𝑓: 0.65 (145433 hom.)
• Consequence: ITGB1 NM_002211.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.278
• Publications: 11 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.672 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITGB1	NM_002211.4	c.154-36A>C		intron_variant	Intron 3 of 15	ENST00000302278.8	NP_002202.2
ITGB1	NM_033668.2	c.154-36A>C		intron_variant	Intron 2 of 15		NP_391988.1
ITGB1	NM_133376.3	c.154-36A>C		intron_variant	Intron 3 of 15		NP_596867.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITGB1	ENST00000302278.8	c.154-36A>C		intron_variant	Intron 3 of 15	1	NM_002211.4	ENSP00000303351.3

Frequencies

GnomAD3 genomes AF: 0.536 AC: 81446 AN: 151882 Hom.: 24925 Cov.: 32

Gnomad AFR AF: 0.225

Gnomad AMI AF: 0.665

Gnomad AMR AF: 0.620

Gnomad ASJ AF: 0.676

Gnomad EAS AF: 0.424

Gnomad SAS AF: 0.661

Gnomad FIN AF: 0.659

Gnomad MID AF: 0.557

Gnomad NFE AF: 0.678

Gnomad OTH AF: 0.549

GnomAD2 exomes AF: 0.628 AC: 137899 AN: 219666 AF XY: 0.636

Gnomad AFR exome AF: 0.220

Gnomad AMR exome AF: 0.683

Gnomad ASJ exome AF: 0.676

Gnomad EAS exome AF: 0.433

Gnomad FIN exome AF: 0.668

Gnomad NFE exome AF: 0.678

Gnomad OTH exome AF: 0.633

GnomAD4 exome AF: 0.649 AC: 438631 AN: 676366 Hom.: 145433 Cov.: 6 AF XY: 0.652 AC XY: 236000 AN XY: 361962

African (AFR) AF: 0.222 AC: 3833 AN: 17282

American (AMR) AF: 0.669 AC: 23277 AN: 34786

Ashkenazi Jewish (ASJ) AF: 0.674 AC: 13257 AN: 19658

East Asian (EAS) AF: 0.441 AC: 15953 AN: 36194

South Asian (SAS) AF: 0.672 AC: 44128 AN: 65642

European-Finnish (FIN) AF: 0.661 AC: 34114 AN: 51594

Middle Eastern (MID) AF: 0.595 AC: 2215 AN: 3724

European-Non Finnish (NFE) AF: 0.679 AC: 280852 AN: 413448

Other (OTH) AF: 0.617 AC: 21002 AN: 34038

GnomAD4 genome AF: 0.536 AC: 81466 AN: 152000 Hom.: 24930 Cov.: 32 AF XY: 0.539 AC XY: 40032 AN XY: 74272

African (AFR) AF: 0.225 AC: 9319 AN: 41436

American (AMR) AF: 0.620 AC: 9478 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.676 AC: 2344 AN: 3470

East Asian (EAS) AF: 0.424 AC: 2192 AN: 5166

South Asian (SAS) AF: 0.661 AC: 3188 AN: 4820

European-Finnish (FIN) AF: 0.659 AC: 6960 AN: 10556

Middle Eastern (MID) AF: 0.548 AC: 161 AN: 294

European-Non Finnish (NFE) AF: 0.678 AC: 46053 AN: 67958

Other (OTH) AF: 0.552 AC: 1166 AN: 2114

Alfa AF: 0.599 Hom.: 5582

Bravo AF: 0.519

Asia WGS AF: 0.569 AC: 1978 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.5
DANN	Benign	0.37
PhyloP100		-0.28
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2256455; hg19: chr10-33219008; COSMIC: COSV56488043; COSMIC: COSV56488043;