chr10-32911570-G-A

Variant names:

• chr10-32911570-G-A
• rs34311462
• NM_002211.4:c.1809C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_002211.4(ITGB1):​c.1809C>T​(p.Asn603Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00143 in 1,614,116 control chromosomes in the GnomAD database, including 34 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0078 (21 hom., cov: 32)
  • Exomes 𝑓: 0.00077 (13 hom.)
• Consequence: ITGB1 NM_002211.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.225
• Publications: 2 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: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 10-32911570-G-A is Benign according to our data. Variant chr10-32911570-G-A is described in ClinVar as [Benign]. Clinvar id is 712042.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.225 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00782 (1190/152252) while in subpopulation AFR AF = 0.0264 (1097/41536). AF 95% confidence interval is 0.0251. There are 21 homozygotes in GnomAd4. There are 588 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 1190 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITGB1	NM_002211.4	c.1809C>T	p.Asn603Asn	synonymous_variant	Exon 13 of 16	ENST00000302278.8	NP_002202.2
ITGB1	NM_033668.2	c.1809C>T	p.Asn603Asn	synonymous_variant	Exon 12 of 16		NP_391988.1
ITGB1	NM_133376.3	c.1809C>T	p.Asn603Asn	synonymous_variant	Exon 13 of 16		NP_596867.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITGB1	ENST00000302278.8	c.1809C>T	p.Asn603Asn	synonymous_variant	Exon 13 of 16	1	NM_002211.4	ENSP00000303351.3

Frequencies

GnomAD3 genomes AF: 0.00781 AC: 1188 AN: 152134 Hom.: 20 Cov.: 32

Gnomad AFR AF: 0.0264

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00465

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.00478

GnomAD2 exomes AF: 0.00194 AC: 489 AN: 251428 AF XY: 0.00153

Gnomad AFR exome AF: 0.0259

Gnomad AMR exome AF: 0.00124

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000163

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000132

Gnomad OTH exome AF: 0.000978

GnomAD4 exome AF: 0.000766 AC: 1120 AN: 1461864 Hom.: 13 Cov.: 32 AF XY: 0.000682 AC XY: 496 AN XY: 727230

African (AFR) AF: 0.0261 AC: 875 AN: 33480

American (AMR) AF: 0.00136 AC: 61 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.000327 AC: 13 AN: 39698

South Asian (SAS) AF: 0.0000348 AC: 3 AN: 86256

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53420

Middle Eastern (MID) AF: 0.00173 AC: 10 AN: 5768

European-Non Finnish (NFE) AF: 0.0000612 AC: 68 AN: 1111986

Other (OTH) AF: 0.00147 AC: 89 AN: 60396

GnomAD4 genome AF: 0.00782 AC: 1190 AN: 152252 Hom.: 21 Cov.: 32 AF XY: 0.00790 AC XY: 588 AN XY: 74440

African (AFR) AF: 0.0264 AC: 1097 AN: 41536

American (AMR) AF: 0.00464 AC: 71 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10600

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.000118 AC: 8 AN: 68030

Other (OTH) AF: 0.00473 AC: 10 AN: 2112

Alfa AF: 0.00407 Hom.: 9

Bravo AF: 0.00908

Asia WGS AF: 0.00231 AC: 8 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.084
DANN	Benign	0.50
PhyloP100		-0.23
Mutation Taster		=100/0	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: rs34311462; hg19: chr10-33200498;