rs4818986

Variant names:

• chr21-44927430-C-T
• rs4818986
• ENST00000441379.5:n.415-195C>T

Variant summary

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

The NM_001127491.3(ITGB2):​c.-4+1224G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.245 in 151,832 control chromosomes in the GnomAD database, including 4,711 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 0.24 (4711 hom., cov: 31)
• Consequence: ITGB2 NM_001127491.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.276
• Publications: 0 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, Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.297 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001127491.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITGB2	NM_001127491.3		c.-4+1224G>A		intron	N/A	NP_001120963.2	P05107
	ITGB2-AS1	NR_038311.1		n.526-195C>T		intron	N/A
	ITGB2-AS1	NR_038312.1		n.526-424C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITGB2-AS1	ENST00000441379.5	TSL:1	n.415-195C>T		intron	N/A
	ITGB2	ENST00000355153.8	TSL:2	c.-4+1224G>A		intron	N/A	ENSP00000347279.4	P05107
	ITGB2	ENST00000397850.6	TSL:5	c.-234+1224G>A		intron	N/A	ENSP00000380948.2	P05107

Frequencies

GnomAD3 genomes AF: 0.245 AC: 37117 AN: 151714 Hom.: 4697 Cov.: 31

Gnomad AFR AF: 0.256

Gnomad AMI AF: 0.309

Gnomad AMR AF: 0.304

Gnomad ASJ AF: 0.273

Gnomad EAS AF: 0.104

Gnomad SAS AF: 0.296

Gnomad FIN AF: 0.191

Gnomad MID AF: 0.259

Gnomad NFE AF: 0.238

Gnomad OTH AF: 0.242

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

GnomAD4 genome AF: 0.245 AC: 37181 AN: 151832 Hom.: 4711 Cov.: 31 AF XY: 0.244 AC XY: 18092 AN XY: 74206

African (AFR) AF: 0.256 AC: 10601 AN: 41360

American (AMR) AF: 0.304 AC: 4644 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.273 AC: 947 AN: 3470

East Asian (EAS) AF: 0.105 AC: 538 AN: 5148

South Asian (SAS) AF: 0.296 AC: 1426 AN: 4810

European-Finnish (FIN) AF: 0.191 AC: 2025 AN: 10578

Middle Eastern (MID) AF: 0.255 AC: 75 AN: 294

European-Non Finnish (NFE) AF: 0.238 AC: 16132 AN: 67902

Other (OTH) AF: 0.244 AC: 512 AN: 2102

Alfa AF: 0.238 Hom.: 550

Bravo AF: 0.255

Asia WGS AF: 0.214 AC: 743 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	5.8
DANN	Benign	0.91
PhyloP100		0.28
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: rs4818986; hg19: chr21-46347345;