10-32947377-T-C

Variant names:

• chr10-32947377-T-C
• rs2488336
• NM_002211.4:c.-1+10768A>G

Variant summary

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

The NM_002211.4(ITGB1):​c.-1+10768A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.455 in 150,414 control chromosomes in the GnomAD database, including 17,870 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 0.46 (17870 hom., cov: 28)
• Consequence: ITGB1 NM_002211.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.420
• Publications: 12 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.579 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002211.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITGB1	NM_002211.4	MANE Select	c.-1+10768A>G		intron	N/A	NP_002202.2
	ITGB1	NM_133376.3		c.-1+10382A>G		intron	N/A	NP_596867.1	P05556-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITGB1	ENST00000302278.8	TSL:1 MANE Select	c.-1+10768A>G		intron	N/A	ENSP00000303351.3	P05556-1
	ITGB1	ENST00000488427.2	TSL:1	c.-162+10768A>G		intron	N/A	ENSP00000417508.2	H7C4K3
	ITGB1	ENST00000966597.1		c.-1+10768A>G		intron	N/A	ENSP00000636656.1

Frequencies

GnomAD3 genomes AF: 0.456 AC: 68479 AN: 150296 Hom.: 17863 Cov.: 28

Gnomad AFR AF: 0.197

Gnomad AMI AF: 0.536

Gnomad AMR AF: 0.555

Gnomad ASJ AF: 0.576

Gnomad EAS AF: 0.272

Gnomad SAS AF: 0.382

Gnomad FIN AF: 0.566

Gnomad MID AF: 0.462

Gnomad NFE AF: 0.584

Gnomad OTH AF: 0.469

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.455 AC: 68500 AN: 150414 Hom.: 17870 Cov.: 28 AF XY: 0.454 AC XY: 33262 AN XY: 73284

African (AFR) AF: 0.196 AC: 8023 AN: 40842

American (AMR) AF: 0.555 AC: 8414 AN: 15160

Ashkenazi Jewish (ASJ) AF: 0.576 AC: 1988 AN: 3452

East Asian (EAS) AF: 0.273 AC: 1394 AN: 5108

South Asian (SAS) AF: 0.382 AC: 1789 AN: 4686

European-Finnish (FIN) AF: 0.566 AC: 5721 AN: 10106

Middle Eastern (MID) AF: 0.462 AC: 135 AN: 292

European-Non Finnish (NFE) AF: 0.584 AC: 39568 AN: 67772

Other (OTH) AF: 0.470 AC: 981 AN: 2088

Alfa AF: 0.530 Hom.: 12028

Bravo AF: 0.444

Asia WGS AF: 0.343 AC: 1194 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.36
DANN	Benign	0.40
PhyloP100		-0.42
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2488336; hg19: chr10-33236305;