rs2153875

Variant names:

• chr10-32901639-C-A
• rs2153875
• NM_002211.4:c.2332-4G>T

Variant summary

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

The NM_002211.4(ITGB1):​c.2332-4G>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.601 in 151,550 control chromosomes in the GnomAD database, including 31,161 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.60 (31161 hom., cov: 30)
  • Exomes 𝑓: 0.73 (382466 hom.)
  • Failed GnomAD Quality Control
• Consequence: ITGB1 NM_002211.4 splice_region, intron
• Scores: Splicing: ADA: 0.00007149
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.30
• Publications: 27 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]

SNORA86 (HGNC:50390): (small nucleolar RNA, H/ACA box 86)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.754 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITGB1	NM_002211.4	c.2332-4G>T		splice_region_variant, intron_variant	Intron 15 of 15	ENST00000302278.8	NP_002202.2
ITGB1	NM_033668.2	c.*7-4G>T		splice_region_variant, intron_variant	Intron 15 of 15		NP_391988.1
ITGB1	NM_133376.3	c.2332-4G>T		splice_region_variant, intron_variant	Intron 15 of 15		NP_596867.1
SNORA86	NR_132768.1	n.-167G>T		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITGB1	ENST00000302278.8	c.2332-4G>T		splice_region_variant, intron_variant	Intron 15 of 15	1	NM_002211.4	ENSP00000303351.3

Frequencies

GnomAD3 genomes AF: 0.602 AC: 91131 AN: 151430 Hom.: 31149 Cov.: 30

Gnomad AFR AF: 0.257

Gnomad AMI AF: 0.692

Gnomad AMR AF: 0.719

Gnomad ASJ AF: 0.797

Gnomad EAS AF: 0.499

Gnomad SAS AF: 0.567

Gnomad FIN AF: 0.744

Gnomad MID AF: 0.646

Gnomad NFE AF: 0.759

Gnomad OTH AF: 0.642

GnomAD2 exomes AF: 0.685 AC: 163951 AN: 239302 AF XY: 0.688

Gnomad AFR exome AF: 0.243

Gnomad AMR exome AF: 0.773

Gnomad ASJ exome AF: 0.793

Gnomad EAS exome AF: 0.501

Gnomad FIN exome AF: 0.737

Gnomad NFE exome AF: 0.758

Gnomad OTH exome AF: 0.706

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.726 AC: 1033279 AN: 1423118 Hom.: 382466 Cov.: 26 AF XY: 0.724 AC XY: 513210 AN XY: 709286

African (AFR) AF: 0.231 AC: 7474 AN: 32382

American (AMR) AF: 0.765 AC: 31274 AN: 40884

Ashkenazi Jewish (ASJ) AF: 0.797 AC: 20208 AN: 25370

East Asian (EAS) AF: 0.501 AC: 19696 AN: 39298

South Asian (SAS) AF: 0.586 AC: 47997 AN: 81852

European-Finnish (FIN) AF: 0.732 AC: 38960 AN: 53200

Middle Eastern (MID) AF: 0.678 AC: 3834 AN: 5654

European-Non Finnish (NFE) AF: 0.758 AC: 822887 AN: 1085420

Other (OTH) AF: 0.693 AC: 40949 AN: 59058

GnomAD4 genome AF: 0.601 AC: 91157 AN: 151550 Hom.: 31161 Cov.: 30 AF XY: 0.601 AC XY: 44525 AN XY: 74080

African (AFR) AF: 0.257 AC: 10571 AN: 41160

American (AMR) AF: 0.719 AC: 10965 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.797 AC: 2758 AN: 3462

East Asian (EAS) AF: 0.500 AC: 2570 AN: 5144

South Asian (SAS) AF: 0.568 AC: 2727 AN: 4802

European-Finnish (FIN) AF: 0.744 AC: 7812 AN: 10496

Middle Eastern (MID) AF: 0.629 AC: 185 AN: 294

European-Non Finnish (NFE) AF: 0.759 AC: 51583 AN: 67936

Other (OTH) AF: 0.645 AC: 1359 AN: 2108

Alfa AF: 0.705 Hom.: 124651

Bravo AF: 0.585

Asia WGS AF: 0.551 AC: 1912 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	7.4
DANN	Benign	0.55
PhyloP100		1.3
Mutation Taster		=95/5	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000071
dbscSNV1_RF	Benign	0.026
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: rs2153875; hg19: chr10-33190567; COSMIC: COSV56480028;