rs199935806

Variant names:

• chr10-32910360-C-A
• rs199935806
• NM_002211.4:c.2027G>T

Your query was ambiguous. Multiple possible variants found:

• chr10-32910360-C-A
• chr10-32910360-C-G
• chr10-32910360-C-T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_002211.4(ITGB1):​c.2027G>T​(p.Arg676Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000132 in 1,599,716 control chromosomes in the GnomAD database, including 2 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00036 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00011 (1 hom.)
• Consequence: ITGB1 NM_002211.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.04
• Publications: 1 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: Likely_benign. The variant received -4 ACMG points.

• BS2: High AC in GnomAd4 at 54 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITGB1	NM_002211.4	c.2027G>T	p.Arg676Leu	missense_variant	Exon 14 of 16	ENST00000302278.8	NP_002202.2
ITGB1	NM_033668.2	c.2027G>T	p.Arg676Leu	missense_variant	Exon 13 of 16		NP_391988.1
ITGB1	NM_133376.3	c.2027G>T	p.Arg676Leu	missense_variant	Exon 14 of 16		NP_596867.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITGB1	ENST00000302278.8	c.2027G>T	p.Arg676Leu	missense_variant	Exon 14 of 16	1	NM_002211.4	ENSP00000303351.3

Frequencies

GnomAD3 genomes AF: 0.000355 AC: 54 AN: 152104 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00308

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.000958

GnomAD2 exomes AF: 0.000184 AC: 46 AN: 250528 AF XY: 0.000133

Gnomad AFR exome AF: 0.0000619

Gnomad AMR exome AF: 0.000899

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000926

Gnomad NFE exome AF: 0.0000882

Gnomad OTH exome AF: 0.000328

GnomAD4 exome AF: 0.000108 AC: 157 AN: 1447612 Hom.: 1 Cov.: 26 AF XY: 0.000101 AC XY: 73 AN XY: 720692

African (AFR) AF: 0.00 AC: 0 AN: 33182

American (AMR) AF: 0.000829 AC: 37 AN: 44628

Ashkenazi Jewish (ASJ) AF: 0.0000384 AC: 1 AN: 26048

East Asian (EAS) AF: 0.00 AC: 0 AN: 39570

South Asian (SAS) AF: 0.00 AC: 0 AN: 85870

European-Finnish (FIN) AF: 0.0000937 AC: 5 AN: 53374

Middle Eastern (MID) AF: 0.000349 AC: 2 AN: 5736

European-Non Finnish (NFE) AF: 0.0000919 AC: 101 AN: 1099242

Other (OTH) AF: 0.000183 AC: 11 AN: 59962

GnomAD4 genome AF: 0.000355 AC: 54 AN: 152104 Hom.: 1 Cov.: 32 AF XY: 0.000458 AC XY: 34 AN XY: 74292

African (AFR) AF: 0.0000241 AC: 1 AN: 41418

American (AMR) AF: 0.00308 AC: 47 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5202

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10606

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 68008

Other (OTH) AF: 0.000958 AC: 2 AN: 2088

Alfa AF: 0.0000868 Hom.: 0

Bravo AF: 0.000461

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000234 AC: 2

ExAC AF: 0.000107 AC: 13

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Apr 12, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2027G>T (p.R676L) alteration is located in exon 13 (coding exon 13) of the ITGB1 gene. This alteration results from a G to T substitution at nucleotide position 2027, causing the arginine (R) at amino acid position 676 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.56
BayesDel_addAF	Benign	-0.033	T
BayesDel_noAF	Uncertain	0.11
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.19	.;T;T
Eigen	Uncertain	0.31
Eigen_PC	Uncertain	0.31
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.94	D;D;.
M_CAP	Uncertain	0.18	D
MetaRNN	Uncertain	0.51	D;D;D
MetaSVM	Uncertain	0.64	D
MutationAssessor	Benign	0.79	N;N;N
PhyloP100		5.0
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	0.10	N;N;N
REVEL	Pathogenic	0.65
Sift	Benign	0.18	T;T;T
Sift4G	Benign	0.56	T;T;T
Polyphen		0.94	P;D;D
Vest4		0.81
MVP		0.93
MPC		1.1
ClinPred		0.096	T
GERP RS		4.7
Varity_R		0.12
gMVP		0.76
Mutation Taster		=57/43	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs199935806; hg19: chr10-33199288;