ENST00000498666.5:n.4488G>T

Variant names:

• chr21-44886246-C-A
• rs684
• ENST00000498666.5:n.4488G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000498666.5(ITGB2):​n.4488G>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000117 in 852,362 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 31)
  • Exomes 𝑓: 0.0000012 (0 hom.)
• Consequence: ITGB2 ENST00000498666.5 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.420
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITGB2	NM_000211.5	c.*122G>T		3_prime_UTR_variant	Exon 16 of 16	ENST00000652462.1	NP_000202.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITGB2	ENST00000652462.1	c.*122G>T		3_prime_UTR_variant	Exon 16 of 16		NM_000211.5	ENSP00000498780.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000117 AC: 1 AN: 852362 Hom.: 0 Cov.: 11 AF XY: 0.00000225 AC XY: 1 AN XY: 445038

African (AFR) AF: 0.00 AC: 0 AN: 21826

American (AMR) AF: 0.00 AC: 0 AN: 41776

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21974

East Asian (EAS) AF: 0.00 AC: 0 AN: 36364

South Asian (SAS) AF: 0.00 AC: 0 AN: 72990

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50826

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3150

European-Non Finnish (NFE) AF: 0.00000177 AC: 1 AN: 563444

Other (OTH) AF: 0.00 AC: 0 AN: 40012

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.4
DANN	Benign	0.59
PhyloP100		-0.42

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

Other links and lift over

dbSNP: rs684; hg19: chr21-46306161;