chr21-44918736-C-T

Variant names:

• chr21-44918736-C-T
• rs9976299
• NM_000211.5:c.-4+2085G>A

Variant summary

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

The NM_000211.5(ITGB2):​c.-4+2085G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.12 in 152,172 control chromosomes in the GnomAD database, including 1,475 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 0.12 (1475 hom., cov: 34)
• Consequence: ITGB2 NM_000211.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.695
• Publications: 7 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 (AFR) allele frequency at 95% confidence interval = 0.214 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.-4+2085G>A		intron	N/A	NP_000202.3	P05107
	ITGB2	NM_001127491.3		c.-3-7951G>A		intron	N/A	NP_001120963.2	P05107
	ITGB2	NM_001303238.2		c.-254+2085G>A		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.-4+2085G>A		intron	N/A	ENSP00000498780.1	A0A494C0X7
	ITGB2	ENST00000302347.10	TSL:1	c.-4+2085G>A		intron	N/A	ENSP00000303242.6	A0AAA9WZN5
	ITGB2	ENST00000397854.7	TSL:1	c.-4+2085G>A		intron	N/A	ENSP00000380952.3	D3DSM0

Frequencies

GnomAD3 genomes AF: 0.120 AC: 18291 AN: 152052 Hom.: 1467 Cov.: 34

Gnomad AFR AF: 0.218

Gnomad AMI AF: 0.0175

Gnomad AMR AF: 0.0674

Gnomad ASJ AF: 0.0795

Gnomad EAS AF: 0.188

Gnomad SAS AF: 0.0437

Gnomad FIN AF: 0.141

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.0740

Gnomad OTH AF: 0.107

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

GnomAD4 genome AF: 0.120 AC: 18328 AN: 152172 Hom.: 1475 Cov.: 34 AF XY: 0.121 AC XY: 9019 AN XY: 74380

African (AFR) AF: 0.218 AC: 9052 AN: 41478

American (AMR) AF: 0.0672 AC: 1028 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0795 AC: 276 AN: 3470

East Asian (EAS) AF: 0.188 AC: 974 AN: 5172

South Asian (SAS) AF: 0.0435 AC: 210 AN: 4826

European-Finnish (FIN) AF: 0.141 AC: 1490 AN: 10604

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

European-Non Finnish (NFE) AF: 0.0740 AC: 5030 AN: 68000

Other (OTH) AF: 0.106 AC: 223 AN: 2112

Alfa AF: 0.0841 Hom.: 774

Bravo AF: 0.121

Asia WGS AF: 0.113 AC: 394 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	0.32
DANN	Benign	0.41
PhyloP100		-0.69
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: rs9976299; hg19: chr21-46338651;