rs2838740

Variant names:

• chr21-44924773-T-C
• rs2838740
• ENST00000441379.5:n.278-2095T>C

Your query was ambiguous. Multiple possible variants found:

• chr21-44924773-T-C
• chr21-44924773-T-G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000441379.5(ITGB2-AS1):​n.278-2095T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.574 in 152,004 control chromosomes in the GnomAD database, including 27,417 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.57 (27417 hom., cov: 32)
• Consequence: ITGB2-AS1 ENST00000441379.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0570
• Publications: 1 publications found

Genes affected

ITGB2-AS1 (HGNC:44304): (ITGB2 antisense RNA 1)

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.834 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITGB2	NM_001127491.3	c.-4+3881A>G		intron_variant	Intron 1 of 15		NP_001120963.2
ITGB2-AS1	NR_038311.1	n.388+1790T>C		intron_variant	Intron 2 of 4
ITGB2-AS1	NR_038312.1	n.388+1790T>C		intron_variant	Intron 2 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITGB2-AS1	ENST00000441379.5	n.278-2095T>C		intron_variant	Intron 1 of 3	1
ITGB2	ENST00000355153.8	c.-4+3881A>G		intron_variant	Intron 1 of 15	2		ENSP00000347279.4
ITGB2	ENST00000397850.6	c.-233-3723A>G		intron_variant	Intron 1 of 16	5		ENSP00000380948.2

Frequencies

GnomAD3 genomes AF: 0.574 AC: 87132 AN: 151886 Hom.: 27356 Cov.: 32

Gnomad AFR AF: 0.841

Gnomad AMI AF: 0.582

Gnomad AMR AF: 0.585

Gnomad ASJ AF: 0.508

Gnomad EAS AF: 0.436

Gnomad SAS AF: 0.390

Gnomad FIN AF: 0.439

Gnomad MID AF: 0.598

Gnomad NFE AF: 0.456

Gnomad OTH AF: 0.549

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.574 AC: 87266 AN: 152004 Hom.: 27417 Cov.: 32 AF XY: 0.570 AC XY: 42327 AN XY: 74252

African (AFR) AF: 0.842 AC: 34920 AN: 41492

American (AMR) AF: 0.586 AC: 8947 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.508 AC: 1763 AN: 3472

East Asian (EAS) AF: 0.438 AC: 2257 AN: 5156

South Asian (SAS) AF: 0.389 AC: 1872 AN: 4808

European-Finnish (FIN) AF: 0.439 AC: 4618 AN: 10528

Middle Eastern (MID) AF: 0.612 AC: 180 AN: 294

European-Non Finnish (NFE) AF: 0.456 AC: 31018 AN: 67954

Other (OTH) AF: 0.550 AC: 1160 AN: 2108

Alfa AF: 0.437 Hom.: 1662

Bravo AF: 0.605

Asia WGS AF: 0.456 AC: 1587 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.1
DANN	Benign	0.26
PhyloP100		0.057
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2838740; hg19: chr21-46344688;