21-44927447-C-T

Variant names:

• chr21-44927447-C-T
• rs4818987
• ENST00000441379.5:n.415-178C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000441379.5(ITGB2-AS1):​n.415-178C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.46 in 151,664 control chromosomes in the GnomAD database, including 16,222 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 0.46 (16222 hom., cov: 30)
• Consequence: ITGB2-AS1 ENST00000441379.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.209
• Publications: 2 publications found

Genes affected

ITGB2-AS1 (HGNC:44304): (ITGB2 antisense RNA 1)

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 Gene-Disease associations (from GenCC):

• leukocyte adhesion deficiency 1

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.508 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITGB2	NM_001127491.3	c.-4+1207G>A		intron_variant	Intron 1 of 15		NP_001120963.2
ITGB2-AS1	NR_038311.1	n.526-178C>T		intron_variant	Intron 3 of 4
ITGB2-AS1	NR_038312.1	n.526-407C>T		intron_variant	Intron 3 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITGB2-AS1	ENST00000441379.5	n.415-178C>T		intron_variant	Intron 2 of 3	1
ITGB2	ENST00000355153.8	c.-4+1207G>A		intron_variant	Intron 1 of 15	2		ENSP00000347279.4
ITGB2	ENST00000397850.6	c.-234+1207G>A		intron_variant	Intron 1 of 16	5		ENSP00000380948.2

Frequencies

GnomAD3 genomes AF: 0.460 AC: 69695 AN: 151548 Hom.: 16192 Cov.: 30

Gnomad AFR AF: 0.483

Gnomad AMI AF: 0.535

Gnomad AMR AF: 0.517

Gnomad ASJ AF: 0.507

Gnomad EAS AF: 0.434

Gnomad SAS AF: 0.388

Gnomad FIN AF: 0.432

Gnomad MID AF: 0.560

Gnomad NFE AF: 0.441

Gnomad OTH AF: 0.457

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

GnomAD4 genome AF: 0.460 AC: 69779 AN: 151664 Hom.: 16222 Cov.: 30 AF XY: 0.460 AC XY: 34089 AN XY: 74128

African (AFR) AF: 0.483 AC: 19960 AN: 41312

American (AMR) AF: 0.518 AC: 7899 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.507 AC: 1760 AN: 3472

East Asian (EAS) AF: 0.436 AC: 2238 AN: 5134

South Asian (SAS) AF: 0.388 AC: 1863 AN: 4802

European-Finnish (FIN) AF: 0.432 AC: 4557 AN: 10546

Middle Eastern (MID) AF: 0.571 AC: 168 AN: 294

European-Non Finnish (NFE) AF: 0.441 AC: 29882 AN: 67826

Other (OTH) AF: 0.458 AC: 965 AN: 2108

Alfa AF: 0.448 Hom.: 1942

Bravo AF: 0.475

Asia WGS AF: 0.416 AC: 1448 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	3.0
DANN	Benign	0.83
PhyloP100		-0.21
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs4818987; hg19: chr21-46347362;