NM_002211.4:c.2331+1294C>A

Variant names:

• chr10-32907074-G-T
• rs200375692
• NM_002211.4:c.2331+1294C>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_002211.4(ITGB1):​c.2331+1294C>A variant causes a intron change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000083 in 1,204,206 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 8.3e-7 (0 hom.)
• Consequence: ITGB1 NM_002211.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.15
• Publications: 0 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITGB1	NM_002211.4	c.2331+1294C>A		intron_variant	Intron 15 of 15	ENST00000302278.8	NP_002202.2
ITGB1	NM_033668.2	c.2401C>A	p.Leu801Ile	missense_variant	Exon 15 of 16		NP_391988.1
ITGB1	NM_133376.3	c.2331+1294C>A		intron_variant	Intron 15 of 15		NP_596867.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITGB1	ENST00000302278.8	c.2331+1294C>A		intron_variant	Intron 15 of 15	1	NM_002211.4	ENSP00000303351.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 8.30e-7 AC: 1 AN: 1204206 Hom.: 0 Cov.: 26 AF XY: 0.00000168 AC XY: 1 AN XY: 597014

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 25888

American (AMR) AF: 0.00 AC: 0 AN: 36288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16780

East Asian (EAS) AF: 0.00 AC: 0 AN: 16746

South Asian (SAS) AF: 0.0000123 AC: 1 AN: 81142

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 32568

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4458

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 946666

Other (OTH) AF: 0.00 AC: 0 AN: 43670

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.060
CADD	Pathogenic	28
DANN	Uncertain	1.0
Eigen	Uncertain	0.53
Eigen_PC	Uncertain	0.64
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.51	T
M_CAP	Uncertain	0.12	D
MetaRNN	Benign	0.29	T
MetaSVM	Benign	-0.76	T
PhyloP100		8.1
PROVEAN	Benign	-0.16	N
REVEL	Uncertain	0.42
Sift	Pathogenic	0.0	D
Polyphen		0.31	B
Vest4		0.43
MutPred		0.24		Gain of methylation at K798 (P = 0.0679);
MVP		0.85
ClinPred		0.93	D
GERP RS		6.0
Mutation Taster		=34/66	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.43		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.43		Position offset: 3

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs200375692; hg19: chr10-33196002;