rs9976299

Positions:

• chr21-44918736-C-T

Variant summary

Our verdict is Benign. Variant got -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

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ITGB2	NM_000211.5	c.-4+2085G>A		intron_variant		ENST00000652462.1	NP_000202.3
ITGB2	NM_001127491.3	c.-3-7951G>A		intron_variant			NP_001120963.2
ITGB2	NM_001303238.2	c.-254+2085G>A		intron_variant			NP_001290167.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ITGB2	ENST00000652462.1	c.-4+2085G>A		intron_variant			NM_000211.5	ENSP00000498780.1

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

Gnomad4 AFR AF: 0.218

Gnomad4 AMR AF: 0.0672

Gnomad4 ASJ AF: 0.0795

Gnomad4 EAS AF: 0.188

Gnomad4 SAS AF: 0.0435

Gnomad4 FIN AF: 0.141

Gnomad4 NFE AF: 0.0740

Gnomad4 OTH AF: 0.106

Alfa AF: 0.0813 Hom.: 618

Bravo AF: 0.121

Asia WGS AF: 0.113 AC: 394 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.32
DANN	Benign	0.41

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs9976299; hg19: chr21-46338651;