rs4607021

chr21-44902572-G-Achr21-44902572-G-Tchr21-44902572-G-C

Variant summary

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

The NM_000211.5(ITGB2):c.499+793C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.666 in 151,266 control chromosomes in the GnomAD database, including 34,651 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 0.67 (34651 hom., cov: 33)
• Consequence: ITGB2 NM_000211.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.470

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=-1.03).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.839 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ITGB2	NM_000211.5	c.499+793C>T		intron_variant		ENST00000652462.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ITGB2	ENST00000652462.1	c.499+793C>T		intron_variant			NM_000211.5	P1

Frequencies

GnomAD3 genomes AF: 0.666 AC: 100649 AN: 151152 Hom.: 34605 Cov.: 33

Gnomad AFR AF: 0.846

Gnomad AMI AF: 0.647

Gnomad AMR AF: 0.625

Gnomad ASJ AF: 0.589

Gnomad EAS AF: 0.404

Gnomad SAS AF: 0.651

Gnomad FIN AF: 0.693

Gnomad MID AF: 0.574

Gnomad NFE AF: 0.588

Gnomad OTH AF: 0.622

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

GnomAD4 genome AF: 0.666 AC: 100750 AN: 151266 Hom.: 34651 Cov.: 33 AF XY: 0.669 AC XY: 49437 AN XY: 73896

Gnomad4 AFR AF: 0.846

Gnomad4 AMR AF: 0.625

Gnomad4 ASJ AF: 0.589

Gnomad4 EAS AF: 0.404

Gnomad4 SAS AF: 0.650

Gnomad4 FIN AF: 0.693

Gnomad4 NFE AF: 0.588

Gnomad4 OTH AF: 0.624

Alfa AF: 0.596 Hom.: 35491

Bravo AF: 0.664

Asia WGS AF: 0.573 AC: 1998 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	0.86
Dann	Benign	0.36
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs4607021; hg19: chr21-46322487;