chr21-44924511-A-G

Variant names:

• chr21-44924511-A-G
• rs2838738
• ENST00000441379.5:n.278-2357A>G

Variant summary

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

The NM_001127491.3(ITGB2):​c.-4+4143T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.55 in 152,050 control chromosomes in the GnomAD database, including 24,645 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 0.55 (24645 hom., cov: 32)
• Consequence: ITGB2 NM_001127491.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.147
• Publications: 14 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, Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.763 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001127491.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITGB2	NM_001127491.3		c.-4+4143T>C		intron	N/A	NP_001120963.2	P05107
	ITGB2-AS1	NR_038311.1		n.388+1528A>G		intron	N/A
	ITGB2-AS1	NR_038312.1		n.388+1528A>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITGB2-AS1	ENST00000441379.5	TSL:1	n.278-2357A>G		intron	N/A
	ITGB2	ENST00000355153.8	TSL:2	c.-4+4143T>C		intron	N/A	ENSP00000347279.4	P05107
	ITGB2	ENST00000397850.6	TSL:5	c.-233-3461T>C		intron	N/A	ENSP00000380948.2	P05107

Frequencies

GnomAD3 genomes AF: 0.550 AC: 83531 AN: 151932 Hom.: 24595 Cov.: 32

Gnomad AFR AF: 0.770

Gnomad AMI AF: 0.582

Gnomad AMR AF: 0.552

Gnomad ASJ AF: 0.495

Gnomad EAS AF: 0.432

Gnomad SAS AF: 0.391

Gnomad FIN AF: 0.438

Gnomad MID AF: 0.579

Gnomad NFE AF: 0.456

Gnomad OTH AF: 0.526

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

GnomAD4 genome AF: 0.550 AC: 83651 AN: 152050 Hom.: 24645 Cov.: 32 AF XY: 0.546 AC XY: 40591 AN XY: 74320

African (AFR) AF: 0.770 AC: 31947 AN: 41464

American (AMR) AF: 0.553 AC: 8444 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.495 AC: 1718 AN: 3468

East Asian (EAS) AF: 0.434 AC: 2245 AN: 5174

South Asian (SAS) AF: 0.391 AC: 1886 AN: 4828

European-Finnish (FIN) AF: 0.438 AC: 4624 AN: 10550

Middle Eastern (MID) AF: 0.592 AC: 174 AN: 294

European-Non Finnish (NFE) AF: 0.456 AC: 30970 AN: 67970

Other (OTH) AF: 0.527 AC: 1113 AN: 2110

Alfa AF: 0.487 Hom.: 80804

Bravo AF: 0.576

Asia WGS AF: 0.447 AC: 1558 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.3
DANN	Benign	0.38
PhyloP100		-0.15
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: rs2838738; hg19: chr21-46344426;