chr21-44915367-T-C

Variant names:

• chr21-44915367-T-C
• rs2838735
• NM_000211.5:c.-3-4582A>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.-3-4582A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.361 in 151,956 control chromosomes in the GnomAD database, including 10,846 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 0.36 (10846 hom., cov: 31)
• Consequence: ITGB2 NM_000211.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.211
• Publications: 12 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, 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.508 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITGB2	NM_000211.5	MANE Select	c.-3-4582A>G		intron	N/A	NP_000202.3	P05107
	ITGB2	NM_001127491.3		c.-3-4582A>G		intron	N/A	NP_001120963.2	P05107
	ITGB2	NM_001303238.2		c.-253-4582A>G		intron	N/A	NP_001290167.1	B4E0R1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITGB2	ENST00000652462.1	MANE Select	c.-3-4582A>G		intron	N/A	ENSP00000498780.1	A0A494C0X7
	ITGB2	ENST00000302347.10	TSL:1	c.-3-4582A>G		intron	N/A	ENSP00000303242.6	A0AAA9WZN5
	ITGB2	ENST00000397854.7	TSL:1	c.-3-4582A>G		intron	N/A	ENSP00000380952.3	D3DSM0

Frequencies

GnomAD3 genomes AF: 0.361 AC: 54797 AN: 151838 Hom.: 10831 Cov.: 31

Gnomad AFR AF: 0.194

Gnomad AMI AF: 0.507

Gnomad AMR AF: 0.517

Gnomad ASJ AF: 0.411

Gnomad EAS AF: 0.455

Gnomad SAS AF: 0.324

Gnomad FIN AF: 0.305

Gnomad MID AF: 0.408

Gnomad NFE AF: 0.426

Gnomad OTH AF: 0.406

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

GnomAD4 genome AF: 0.361 AC: 54809 AN: 151956 Hom.: 10846 Cov.: 31 AF XY: 0.358 AC XY: 26607 AN XY: 74254

African (AFR) AF: 0.193 AC: 8016 AN: 41446

American (AMR) AF: 0.518 AC: 7901 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.411 AC: 1427 AN: 3468

East Asian (EAS) AF: 0.456 AC: 2345 AN: 5146

South Asian (SAS) AF: 0.323 AC: 1555 AN: 4820

European-Finnish (FIN) AF: 0.305 AC: 3230 AN: 10574

Middle Eastern (MID) AF: 0.395 AC: 116 AN: 294

European-Non Finnish (NFE) AF: 0.426 AC: 28910 AN: 67932

Other (OTH) AF: 0.402 AC: 848 AN: 2108

Alfa AF: 0.406 Hom.: 41307

Bravo AF: 0.370

Asia WGS AF: 0.408 AC: 1417 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	4.3
DANN	Benign	0.45
PhyloP100		-0.21
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: rs2838735; hg19: chr21-46335282;