rs2838730

chr21-44899577-G-A

Variant summary

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

The NM_000211.5(ITGB2):c.898-415C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.499 in 152,016 control chromosomes in the GnomAD database, including 19,789 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 0.50 (19789 hom., cov: 33)
• Consequence: ITGB2 NM_000211.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.30

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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.638 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ITGB2	NM_000211.5	c.898-415C>T		intron_variant		ENST00000652462.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ITGB2	ENST00000652462.1	c.898-415C>T		intron_variant			NM_000211.5	P1

Frequencies

GnomAD3 genomes AF: 0.498 AC: 75692 AN: 151898 Hom.: 19745 Cov.: 33

Gnomad AFR AF: 0.644

Gnomad AMI AF: 0.455

Gnomad AMR AF: 0.516

Gnomad ASJ AF: 0.487

Gnomad EAS AF: 0.506

Gnomad SAS AF: 0.450

Gnomad FIN AF: 0.372

Gnomad MID AF: 0.601

Gnomad NFE AF: 0.428

Gnomad OTH AF: 0.533

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

GnomAD4 genome AF: 0.499 AC: 75796 AN: 152016 Hom.: 19789 Cov.: 33 AF XY: 0.497 AC XY: 36903 AN XY: 74278

Gnomad4 AFR AF: 0.645

Gnomad4 AMR AF: 0.517

Gnomad4 ASJ AF: 0.487

Gnomad4 EAS AF: 0.505

Gnomad4 SAS AF: 0.450

Gnomad4 FIN AF: 0.372

Gnomad4 NFE AF: 0.428

Gnomad4 OTH AF: 0.531

Alfa AF: 0.450 Hom.: 8621

Bravo AF: 0.515

Asia WGS AF: 0.471 AC: 1641 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	0.97
Dann	Benign	0.78

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs2838730; hg19: chr21-46319492; COSMIC: COSV56608863; COSMIC: COSV56608863;