10-32911903-T-C

Variant names:

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

Variant summary

Our verdict is Likely benign. Variant got -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. 13/21 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

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 Likely_benign. Variant got -6 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITGB1	NM_002211.4	c.1691A>G	p.Asn564Ser	missense_variant	Exon 12 of 16	ENST00000302278.8	NP_002202.2
ITGB1	NM_033668.2	c.1691A>G	p.Asn564Ser	missense_variant	Exon 11 of 16		NP_391988.1
ITGB1	NM_133376.3	c.1691A>G	p.Asn564Ser	missense_variant	Exon 12 of 16		NP_596867.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITGB1	ENST00000302278.8	c.1691A>G	p.Asn564Ser	missense_variant	Exon 12 of 16	1	NM_002211.4	ENSP00000303351.3

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

GnomAD3 exomes AF: 0.0000240 AC: 6 AN: 250162 Hom.: 0 AF XY: 0.0000370 AC XY: 5 AN XY: 135170

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 SAS exome AF: 0.0000329

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

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000504

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.0000377

Gnomad4 NFE exome AF: 0.0000495

Gnomad4 OTH exome AF: 0.000133

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

Gnomad4 AFR AF: 0.0000483

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000103

Gnomad4 OTH AF: 0.000478

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

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 27, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1691A>G (p.N564S) alteration is located in exon 11 (coding exon 11) of the ITGB1 gene. This alteration results from a A to G substitution at nucleotide position 1691, causing the asparagine (N) at amino acid position 564 to be replaced by a serine (S). 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	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;T
Eigen	Benign	-0.091
Eigen_PC	Benign	0.12
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.89	D;D;.
M_CAP	Benign	0.050	D
MetaRNN	Benign	0.17	T;T;T
MetaSVM	Uncertain	-0.0022	T
MutationAssessor	Benign	1.1	L;L;L
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	-1.6	N;N;N
REVEL	Benign	0.26
Sift	Benign	0.095	T;T;T
Sift4G	Benign	0.24	T;T;T
Polyphen		0.0	B;B;B
Vest4		0.27
MutPred		0.31		Gain of glycosylation at N564 (P = 0.0423);Gain of glycosylation at N564 (P = 0.0423);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

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