NM_000211.5:c.-3-4880A>G

Variant names:

• chr21-44915665-T-C
• rs2838737
• NM_000211.5:c.-3-4880A>G

Variant summary

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

The NM_000211.5(ITGB2):​c.-3-4880A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.799 in 152,084 control chromosomes in the GnomAD database, including 49,020 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 0.80 (49020 hom., cov: 31)
• Consequence: ITGB2 NM_000211.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.87
• Publications: 17 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.886 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000211.5. 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.-3-4880A>G		intron	N/A	NP_000202.3
	ITGB2	NM_001127491.3		c.-3-4880A>G		intron	N/A	NP_001120963.2
	ITGB2	NM_001303238.2		c.-253-4880A>G		intron	N/A	NP_001290167.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITGB2	ENST00000652462.1	MANE Select	c.-3-4880A>G		intron	N/A	ENSP00000498780.1
	ITGB2	ENST00000302347.10	TSL:1	c.-3-4880A>G		intron	N/A	ENSP00000303242.6
	ITGB2	ENST00000397854.7	TSL:1	c.-3-4880A>G		intron	N/A	ENSP00000380952.3

Frequencies

GnomAD3 genomes AF: 0.799 AC: 121483 AN: 151966 Hom.: 48983 Cov.: 31

Gnomad AFR AF: 0.686

Gnomad AMI AF: 0.797

Gnomad AMR AF: 0.870

Gnomad ASJ AF: 0.857

Gnomad EAS AF: 0.725

Gnomad SAS AF: 0.908

Gnomad FIN AF: 0.806

Gnomad MID AF: 0.810

Gnomad NFE AF: 0.846

Gnomad OTH AF: 0.817

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

GnomAD4 genome AF: 0.799 AC: 121573 AN: 152084 Hom.: 49020 Cov.: 31 AF XY: 0.801 AC XY: 59583 AN XY: 74342

African (AFR) AF: 0.686 AC: 28445 AN: 41446

American (AMR) AF: 0.870 AC: 13303 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.857 AC: 2975 AN: 3470

East Asian (EAS) AF: 0.725 AC: 3743 AN: 5162

South Asian (SAS) AF: 0.908 AC: 4383 AN: 4826

European-Finnish (FIN) AF: 0.806 AC: 8533 AN: 10586

Middle Eastern (MID) AF: 0.803 AC: 236 AN: 294

European-Non Finnish (NFE) AF: 0.846 AC: 57508 AN: 67998

Other (OTH) AF: 0.817 AC: 1722 AN: 2108

Alfa AF: 0.834 Hom.: 234087

Bravo AF: 0.794

Asia WGS AF: 0.836 AC: 2909 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.20
DANN	Benign	0.38
PhyloP100		-3.9
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: rs2838737; hg19: chr21-46335580;