rs1316757

Positions:

• chr10-32908269-A-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000302278.8(ITGB1):​c.2331+99T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.108 in 1,154,740 control chromosomes in the GnomAD database, including 8,218 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 0.090 (890 hom., cov: 32)
  • Exomes 𝑓: 0.11 (7328 hom.)
• Consequence: ITGB1 ENST00000302278.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0980

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• 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/exons	MANE	Protein	UniProt
ITGB1	NM_002211.4	c.2331+99T>G		intron_variant		ENST00000302278.8	NP_002202.2
ITGB1	NM_033668.2	c.2331+99T>G		intron_variant			NP_391988.1
ITGB1	NM_133376.3	c.2331+99T>G		intron_variant			NP_596867.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ITGB1	ENST00000302278.8	c.2331+99T>G		intron_variant		1	NM_002211.4	ENSP00000303351	P4

Frequencies

GnomAD3 genomes AF: 0.0906 AC: 13787 AN: 152144 Hom.: 896 Cov.: 32

Gnomad AFR AF: 0.0310

Gnomad AMI AF: 0.0417

Gnomad AMR AF: 0.0874

Gnomad ASJ AF: 0.0904

Gnomad EAS AF: 0.328

Gnomad SAS AF: 0.135

Gnomad FIN AF: 0.122

Gnomad MID AF: 0.121

Gnomad NFE AF: 0.102

Gnomad OTH AF: 0.0948

GnomAD4 exome AF: 0.111 AC: 111472 AN: 1002478 Hom.: 7328 AF XY: 0.113 AC XY: 57980 AN XY: 515362

Gnomad4 AFR exome AF: 0.0274

Gnomad4 AMR exome AF: 0.0794

Gnomad4 ASJ exome AF: 0.0933

Gnomad4 EAS exome AF: 0.310

Gnomad4 SAS exome AF: 0.129

Gnomad4 FIN exome AF: 0.125

Gnomad4 NFE exome AF: 0.103

Gnomad4 OTH exome AF: 0.107

GnomAD4 genome AF: 0.0904 AC: 13765 AN: 152262 Hom.: 890 Cov.: 32 AF XY: 0.0931 AC XY: 6934 AN XY: 74472

Gnomad4 AFR AF: 0.0309

Gnomad4 AMR AF: 0.0870

Gnomad4 ASJ AF: 0.0904

Gnomad4 EAS AF: 0.327

Gnomad4 SAS AF: 0.134

Gnomad4 FIN AF: 0.122

Gnomad4 NFE AF: 0.102

Gnomad4 OTH AF: 0.0934

Alfa AF: 0.0991 Hom.: 805

Bravo AF: 0.0850

Asia WGS AF: 0.166 AC: 577 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	3.3
DANN	Benign	0.73

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: rs1316757; hg19: chr10-33197197; COSMIC: COSV56480845;