rs5030667

Variant names:

• chr21-44910752-G-A
• rs5030667
• NM_000211.5:c.31C>T

Your query was ambiguous. Multiple possible variants found:

• chr21-44910752-G-A
• chr21-44910752-G-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001303238.2(ITGB2):​c.-220C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0232 in 1,614,022 control chromosomes in the GnomAD database, including 563 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.019 (44 hom., cov: 33)
  • Exomes 𝑓: 0.024 (519 hom.)
• Consequence: ITGB2 NM_001303238.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.0630

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 21-44910752-G-A is Benign according to our data. Variant chr21-44910752-G-A is described in ClinVar as [Benign]. Clinvar id is 340183.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-44910752-G-A is described in Lovd as [Benign].
• BA1: GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.103 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITGB2	NM_000211.5	c.31C>T	p.Leu11Leu	synonymous_variant	Exon 2 of 16	ENST00000652462.1	NP_000202.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITGB2	ENST00000652462.1	c.31C>T	p.Leu11Leu	synonymous_variant	Exon 2 of 16		NM_000211.5	ENSP00000498780.1

Frequencies

GnomAD3 genomes AF: 0.0194 AC: 2951 AN: 152234 Hom.: 44 Cov.: 33

Gnomad AFR AF: 0.0152

Gnomad AMI AF: 0.0352

Gnomad AMR AF: 0.0168

Gnomad ASJ AF: 0.0294

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0139

Gnomad FIN AF: 0.0125

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.0243

Gnomad OTH AF: 0.0220

GnomAD3 exomes AF: 0.0202 AC: 5045 AN: 250206 Hom.: 85 AF XY: 0.0209 AC XY: 2824 AN XY: 135384

Gnomad AFR exome AF: 0.0145

Gnomad AMR exome AF: 0.0138

Gnomad ASJ exome AF: 0.0296

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0127

Gnomad FIN exome AF: 0.0151

Gnomad NFE exome AF: 0.0277

Gnomad OTH exome AF: 0.0315

GnomAD4 exome AF: 0.0236 AC: 34517 AN: 1461670 Hom.: 519 Cov.: 31 AF XY: 0.0236 AC XY: 17196 AN XY: 727132

Gnomad4 AFR exome AF: 0.0167

Gnomad4 AMR exome AF: 0.0146

Gnomad4 ASJ exome AF: 0.0288

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0131

Gnomad4 FIN exome AF: 0.0148

Gnomad4 NFE exome AF: 0.0256

Gnomad4 OTH exome AF: 0.0252

GnomAD4 genome AF: 0.0194 AC: 2950 AN: 152352 Hom.: 44 Cov.: 33 AF XY: 0.0186 AC XY: 1383 AN XY: 74492

Gnomad4 AFR AF: 0.0151

Gnomad4 AMR AF: 0.0168

Gnomad4 ASJ AF: 0.0294

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0137

Gnomad4 FIN AF: 0.0125

Gnomad4 NFE AF: 0.0243

Gnomad4 OTH AF: 0.0218

Alfa AF: 0.0247 Hom.: 27

Bravo AF: 0.0202

Asia WGS AF: 0.00520 AC: 20 AN: 3478

EpiCase AF: 0.0315

EpiControl AF: 0.0325

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Leukocyte adhesion deficiency 1 Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jan 12, 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. -

not specified Benign:1

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: MAF -

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	2.0
DANN	Benign	0.67
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs5030667; hg19: chr21-46330667;