rs760452

Variant names:

• chr21-44920726-T-C
• rs760452
• NM_000211.5:c.-4+95A>G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000211.5(ITGB2):​c.-4+95A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.568 in 152,268 control chromosomes in the GnomAD database, including 27,373 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 0.57 (27362 hom., cov: 33)
  • Exomes 𝑓: 0.44 (11 hom.)
• Consequence: ITGB2 NM_000211.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.04

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.864 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITGB2	NM_000211.5	c.-4+95A>G		intron_variant	Intron 1 of 15	ENST00000652462.1	NP_000202.3
ITGB2	NM_001127491.3	c.-4+7928A>G		intron_variant	Intron 1 of 15		NP_001120963.2
ITGB2	NM_001303238.2	c.-254+95A>G		intron_variant	Intron 1 of 15		NP_001290167.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITGB2	ENST00000652462.1	c.-4+95A>G		intron_variant	Intron 1 of 15		NM_000211.5	ENSP00000498780.1

Frequencies

GnomAD3 genomes AF: 0.568 AC: 86278 AN: 152026 Hom.: 27294 Cov.: 33

Gnomad AFR AF: 0.871

Gnomad AMI AF: 0.487

Gnomad AMR AF: 0.513

Gnomad ASJ AF: 0.497

Gnomad EAS AF: 0.434

Gnomad SAS AF: 0.389

Gnomad FIN AF: 0.442

Gnomad MID AF: 0.592

Gnomad NFE AF: 0.443

Gnomad OTH AF: 0.537

GnomAD4 exome AF: 0.444 AC: 55 AN: 124 Hom.: 11 AF XY: 0.476 AC XY: 40 AN XY: 84

Gnomad4 AFR exome AF: 1.00

Gnomad4 AMR exome AF: 0.500

Gnomad4 EAS exome AF: 0.500

Gnomad4 SAS exome AF: 0.333

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.418

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.568 AC: 86414 AN: 152144 Hom.: 27362 Cov.: 33 AF XY: 0.564 AC XY: 41967 AN XY: 74384

Gnomad4 AFR AF: 0.871

Gnomad4 AMR AF: 0.513

Gnomad4 ASJ AF: 0.497

Gnomad4 EAS AF: 0.436

Gnomad4 SAS AF: 0.389

Gnomad4 FIN AF: 0.442

Gnomad4 NFE AF: 0.443

Gnomad4 OTH AF: 0.538

Alfa AF: 0.510 Hom.: 2751

Bravo AF: 0.591

Asia WGS AF: 0.453 AC: 1579 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.92
DANN	Benign	0.45

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs760452; hg19: chr21-46340641;