rs201792925

Variant names:

• chr10-32911903-T-C
• rs201792925
• NM_002211.4:c.1691A>G

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_002211.4(ITGB1):​c.1691A>G​(p.Asn564Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000484 in 1,612,560 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000047 (0 hom.)
• Consequence: ITGB1 NM_002211.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.90
• Publications: 3 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 -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.17315483).
• BS2: High AC in GnomAd4 at 10 AD gene.

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.1691A>G	p.Asn564Ser	missense	Exon 12 of 16	NP_002202.2
	ITGB1	NM_033668.2		c.1691A>G	p.Asn564Ser	missense	Exon 11 of 16	NP_391988.1	P05556-5
	ITGB1	NM_133376.3		c.1691A>G	p.Asn564Ser	missense	Exon 12 of 16	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.1691A>G	p.Asn564Ser	missense	Exon 12 of 16	ENSP00000303351.3	P05556-1
	ITGB1	ENST00000488427.2	TSL:1	c.1520A>G	p.Asn507Ser	missense	Exon 12 of 16	ENSP00000417508.2	H7C4K3
	ITGB1	ENST00000966597.1		c.1928A>G	p.Asn643Ser	missense	Exon 13 of 17	ENSP00000636656.1

Frequencies

GnomAD3 genomes AF: 0.0000657 AC: 10 AN: 152190 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.000103

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.0000240 AC: 6 AN: 250162 AF XY: 0.0000370

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000354

Gnomad OTH exome AF: 0.000164

GnomAD4 exome AF: 0.0000466 AC: 68 AN: 1460370 Hom.: 0 Cov.: 32 AF XY: 0.0000523 AC XY: 38 AN XY: 726452

African (AFR) AF: 0.00 AC: 0 AN: 33472

American (AMR) AF: 0.00 AC: 0 AN: 44682

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26062

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39698

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86070

European-Finnish (FIN) AF: 0.0000377 AC: 2 AN: 53054

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.0000495 AC: 55 AN: 1111214

Other (OTH) AF: 0.000133 AC: 8 AN: 60352

GnomAD4 genome AF: 0.0000657 AC: 10 AN: 152190 Hom.: 0 Cov.: 33 AF XY: 0.0000672 AC XY: 5 AN XY: 74350

African (AFR) AF: 0.0000483 AC: 2 AN: 41440

American (AMR) AF: 0.00 AC: 0 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5200

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000103 AC: 7 AN: 68034

Other (OTH) AF: 0.000478 AC: 1 AN: 2092

Alfa AF: 0.000108 Hom.: 0

Bravo AF: 0.0000189

ExAC AF: 0.00000824 AC: 1

EpiCase AF: 0.0000545

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.088
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.50	T
Eigen	Benign	-0.091
Eigen_PC	Benign	0.12
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.050	D
MetaRNN	Benign	0.17	T
MetaSVM	Uncertain	-0.0022	T
MutationAssessor	Benign	1.1	L
PhyloP100		3.9
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.26
Sift	Benign	0.095	T
Sift4G	Benign	0.24	T
Polyphen		0.0	B
Vest4		0.27
MutPred		0.31		Gain of glycosylation at N564 (P = 0.0423)
MVP		0.80
MPC		0.62
ClinPred		0.17	T
GERP RS		5.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.11
gMVP		0.60
Mutation Taster		=73/27	polymorphism

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: rs201792925; hg19: chr10-33200831; COSMIC: COSV56485418; COSMIC: COSV56485418;