rs5030670

Variant names:

• chr21-44900488-C-T
• rs5030670
• NM_000211.5:c.742-13G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000211.5(ITGB2):​c.742-13G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.145 in 1,613,112 control chromosomes in the GnomAD database, including 18,231 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.12 (1291 hom., cov: 33)
  • Exomes 𝑓: 0.15 (16940 hom.)
• Consequence: ITGB2 NM_000211.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7 O:1
• Conservation: PhyloP100: -1.84
• Publications: 8 publications found

Genes affected

ITGB2 (HGNC:6155): (integrin subunit beta 2) This gene encodes an integrin beta chain, which combines with multiple different alpha chains to form different integrin heterodimers. Integrins are integral cell-surface proteins that participate in cell adhesion as well as cell-surface mediated signalling. The encoded protein plays an important role in immune response and defects in this gene cause leukocyte adhesion deficiency. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2014]

ITGB2 Gene-Disease associations (from GenCC):

• leukocyte adhesion deficiency 1

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 21-44900488-C-T is Benign according to our data. Variant chr21-44900488-C-T is described in ClinVar as Benign. ClinVar VariationId is 100760.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.156 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITGB2	NM_000211.5	c.742-13G>A		intron_variant	Intron 6 of 15	ENST00000652462.1	NP_000202.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITGB2	ENST00000652462.1	c.742-13G>A		intron_variant	Intron 6 of 15		NM_000211.5	ENSP00000498780.1

Frequencies

GnomAD3 genomes AF: 0.121 AC: 18424 AN: 152084 Hom.: 1291 Cov.: 33

Gnomad AFR AF: 0.0644

Gnomad AMI AF: 0.108

Gnomad AMR AF: 0.101

Gnomad ASJ AF: 0.134

Gnomad EAS AF: 0.0288

Gnomad SAS AF: 0.100

Gnomad FIN AF: 0.176

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.159

Gnomad OTH AF: 0.142

GnomAD2 exomes AF: 0.124 AC: 31148 AN: 250310 AF XY: 0.128

Gnomad AFR exome AF: 0.0597

Gnomad AMR exome AF: 0.0692

Gnomad ASJ exome AF: 0.136

Gnomad EAS exome AF: 0.0302

Gnomad FIN exome AF: 0.177

Gnomad NFE exome AF: 0.162

Gnomad OTH exome AF: 0.133

GnomAD4 exome AF: 0.148 AC: 215805 AN: 1460910 Hom.: 16940 Cov.: 35 AF XY: 0.147 AC XY: 106668 AN XY: 726742

African (AFR) AF: 0.0589 AC: 1970 AN: 33468

American (AMR) AF: 0.0723 AC: 3234 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.134 AC: 3494 AN: 26126

East Asian (EAS) AF: 0.0228 AC: 905 AN: 39694

South Asian (SAS) AF: 0.0954 AC: 8224 AN: 86234

European-Finnish (FIN) AF: 0.173 AC: 9211 AN: 53250

Middle Eastern (MID) AF: 0.110 AC: 604 AN: 5476

European-Non Finnish (NFE) AF: 0.162 AC: 179987 AN: 1111612

Other (OTH) AF: 0.135 AC: 8176 AN: 60342

GnomAD4 genome AF: 0.121 AC: 18419 AN: 152202 Hom.: 1291 Cov.: 33 AF XY: 0.120 AC XY: 8914 AN XY: 74408

African (AFR) AF: 0.0643 AC: 2673 AN: 41556

American (AMR) AF: 0.101 AC: 1548 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.134 AC: 465 AN: 3468

East Asian (EAS) AF: 0.0289 AC: 149 AN: 5164

South Asian (SAS) AF: 0.0999 AC: 482 AN: 4824

European-Finnish (FIN) AF: 0.176 AC: 1866 AN: 10598

Middle Eastern (MID) AF: 0.122 AC: 36 AN: 294

European-Non Finnish (NFE) AF: 0.159 AC: 10806 AN: 67978

Other (OTH) AF: 0.140 AC: 296 AN: 2114

Alfa AF: 0.140 Hom.: 2622

Bravo AF: 0.113

Asia WGS AF: 0.0560 AC: 194 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:7 Other:1

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Leukocyte adhesion deficiency 1 Benign:3 Other:1

-

Genomic Research Center, Shahid Beheshti University of Medical Sciences

Significance: not provided

Review Status: no classification provided

Collection Method: literature only

- -

Aug 19, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified Benign:2

Jan 24, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 26% of patients studied by a panel of primary immunodeficiencies. Number of patients: 25. Only high quality variants are reported. -

Mar 28, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Mar 03, 2015

GeneDx

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	-0.89
CADD	Benign	0.11
DANN	Benign	0.59
PhyloP100		-1.8
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs5030670; hg19: chr21-46320403; COSMIC: COSV56610895; COSMIC: COSV56610895;