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. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The ENST00000652462.1(ITGB2):​c.31C>T​(p.Leu11Leu) variant causes a synonymous 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 ENST00000652462.1 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.0630
• Publications: 4 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 -21 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 VariationId is 340183.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.063 with no splicing effect.
• BA1: GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.103 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000652462.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITGB2	NM_000211.5	MANE Select	c.31C>T	p.Leu11Leu	synonymous	Exon 2 of 16	NP_000202.3
	ITGB2	NM_001303238.2		c.-220C>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 16	NP_001290167.1
	ITGB2	NM_001127491.3		c.31C>T	p.Leu11Leu	synonymous	Exon 2 of 16	NP_001120963.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITGB2	ENST00000652462.1	MANE Select	c.31C>T	p.Leu11Leu	synonymous	Exon 2 of 16	ENSP00000498780.1
	ITGB2	ENST00000302347.10	TSL:1	c.31C>T	p.Leu11Leu	synonymous	Exon 2 of 17	ENSP00000303242.6
	ITGB2	ENST00000397852.5	TSL:1	c.31C>T	p.Leu11Leu	synonymous	Exon 1 of 15	ENSP00000380950.1

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

GnomAD2 exomes AF: 0.0202 AC: 5045 AN: 250206 AF XY: 0.0209

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 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

African (AFR) AF: 0.0167 AC: 559 AN: 33478

American (AMR) AF: 0.0146 AC: 654 AN: 44692

Ashkenazi Jewish (ASJ) AF: 0.0288 AC: 753 AN: 26114

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.0131 AC: 1126 AN: 86230

European-Finnish (FIN) AF: 0.0148 AC: 791 AN: 53368

Middle Eastern (MID) AF: 0.110 AC: 632 AN: 5768

European-Non Finnish (NFE) AF: 0.0256 AC: 28482 AN: 1111936

Other (OTH) AF: 0.0252 AC: 1520 AN: 60390

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

African (AFR) AF: 0.0151 AC: 630 AN: 41586

American (AMR) AF: 0.0168 AC: 257 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.0294 AC: 102 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.0137 AC: 66 AN: 4832

European-Finnish (FIN) AF: 0.0125 AC: 133 AN: 10628

Middle Eastern (MID) AF: 0.0986 AC: 29 AN: 294

European-Non Finnish (NFE) AF: 0.0243 AC: 1655 AN: 68016

Other (OTH) AF: 0.0218 AC: 46 AN: 2114

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

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	Leukocyte adhesion deficiency 1 (2)
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	2.0
DANN	Benign	0.67
PhyloP100		-0.063
PromoterAI		0.017	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=100/0	polymorphism (auto)

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: rs5030667; hg19: chr21-46330667;