rs1474552

Variant names:

• chr21-44917375-T-C
• rs1474552
• NM_000211.5:c.-4+3446A>G

Your query was ambiguous. Multiple possible variants found:

• chr21-44917375-T-C
• chr21-44917375-T-G

Variant summary

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

The NM_000211.5(ITGB2):​c.-4+3446A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.183 in 152,206 control chromosomes in the GnomAD database, including 3,576 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 0.18 (3576 hom., cov: 33)
• Consequence: ITGB2 NM_000211.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.100
• Publications: 13 publications found

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 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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.34 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITGB2	NM_000211.5	c.-4+3446A>G		intron_variant	Intron 1 of 15	ENST00000652462.1	NP_000202.3
ITGB2	NM_001127491.3	c.-3-6590A>G		intron_variant	Intron 1 of 15		NP_001120963.2
ITGB2	NM_001303238.2	c.-254+3446A>G		intron_variant	Intron 1 of 15		NP_001290167.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITGB2	ENST00000652462.1	c.-4+3446A>G		intron_variant	Intron 1 of 15		NM_000211.5	ENSP00000498780.1

Frequencies

GnomAD3 genomes AF: 0.183 AC: 27843 AN: 152088 Hom.: 3568 Cov.: 33

Gnomad AFR AF: 0.345

Gnomad AMI AF: 0.0855

Gnomad AMR AF: 0.247

Gnomad ASJ AF: 0.120

Gnomad EAS AF: 0.209

Gnomad SAS AF: 0.136

Gnomad FIN AF: 0.121

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.0866

Gnomad OTH AF: 0.162

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

GnomAD4 genome AF: 0.183 AC: 27891 AN: 152206 Hom.: 3576 Cov.: 33 AF XY: 0.185 AC XY: 13788 AN XY: 74428

African (AFR) AF: 0.345 AC: 14313 AN: 41484

American (AMR) AF: 0.247 AC: 3785 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.120 AC: 415 AN: 3470

East Asian (EAS) AF: 0.210 AC: 1087 AN: 5186

South Asian (SAS) AF: 0.136 AC: 656 AN: 4826

European-Finnish (FIN) AF: 0.121 AC: 1278 AN: 10602

Middle Eastern (MID) AF: 0.170 AC: 50 AN: 294

European-Non Finnish (NFE) AF: 0.0866 AC: 5889 AN: 68022

Other (OTH) AF: 0.161 AC: 340 AN: 2116

Alfa AF: 0.118 Hom.: 2760

Bravo AF: 0.199

Asia WGS AF: 0.171 AC: 594 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	8.4
DANN	Benign	0.85
PhyloP100		-0.10
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: rs1474552; hg19: chr21-46337290;