rs180318

Positions:

• chr21-44887580-T-C
• chr21-44887580-T-A

Variant summary

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

The NM_000211.5(ITGB2):​c.2081-678A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.696 in 151,652 control chromosomes in the GnomAD database, including 38,096 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 0.70 (38096 hom., cov: 31)
• Consequence: ITGB2 NM_000211.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.73

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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.884 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ITGB2	NM_000211.5	c.2081-678A>G		intron_variant		ENST00000652462.1	NP_000202.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ITGB2	ENST00000652462.1	c.2081-678A>G		intron_variant			NM_000211.5	ENSP00000498780.1

Frequencies

GnomAD3 genomes AF: 0.696 AC: 105466 AN: 151534 Hom.: 38031 Cov.: 31

Gnomad AFR AF: 0.891

Gnomad AMI AF: 0.452

Gnomad AMR AF: 0.627

Gnomad ASJ AF: 0.613

Gnomad EAS AF: 0.809

Gnomad SAS AF: 0.689

Gnomad FIN AF: 0.619

Gnomad MID AF: 0.662

Gnomad NFE AF: 0.604

Gnomad OTH AF: 0.701

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

GnomAD4 genome AF: 0.696 AC: 105597 AN: 151652 Hom.: 38096 Cov.: 31 AF XY: 0.696 AC XY: 51602 AN XY: 74110

Gnomad4 AFR AF: 0.892

Gnomad4 AMR AF: 0.626

Gnomad4 ASJ AF: 0.613

Gnomad4 EAS AF: 0.808

Gnomad4 SAS AF: 0.689

Gnomad4 FIN AF: 0.619

Gnomad4 NFE AF: 0.604

Gnomad4 OTH AF: 0.706

Alfa AF: 0.638 Hom.: 7069

Bravo AF: 0.707

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.36
DANN	Benign	0.37

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: rs180318; hg19: chr21-46307495; COSMIC: COSV56612321;