21-44885998-C-A

Position:

• chr21-44885998-C-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_000211.5(ITGB2):​c.*370G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0111 in 330,750 control chromosomes in the GnomAD database, including 35 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.011 (16 hom., cov: 33)
  • Exomes 𝑓: 0.011 (19 hom.)
• Consequence: ITGB2 NM_000211.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.164

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 21-44885998-C-A is Benign according to our data. Variant chr21-44885998-C-A is described in ClinVar as [Benign]. Clinvar id is 895891.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.011 (1668/152076) while in subpopulation NFE AF= 0.0167 (1137/68010). AF 95% confidence interval is 0.0159. There are 16 homozygotes in gnomad4. There are 787 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 16 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ITGB2	NM_000211.5	c.*370G>T		3_prime_UTR_variant	16/16	ENST00000652462.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ITGB2	ENST00000652462.1	c.*370G>T		3_prime_UTR_variant	16/16		NM_000211.5	P1

Frequencies

GnomAD3 genomes AF: 0.0110 AC: 1670 AN: 151958 Hom.: 16 Cov.: 33

Gnomad AFR AF: 0.00322

Gnomad AMI AF: 0.00439

Gnomad AMR AF: 0.0113

Gnomad ASJ AF: 0.0190

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.0119

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0167

Gnomad OTH AF: 0.0129

GnomAD4 exome AF: 0.0111 AC: 1987 AN: 178674 Hom.: 19 Cov.: 0 AF XY: 0.0102 AC XY: 983 AN XY: 96304

Gnomad4 AFR exome AF: 0.00184

Gnomad4 AMR exome AF: 0.00746

Gnomad4 ASJ exome AF: 0.0160

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00106

Gnomad4 FIN exome AF: 0.0103

Gnomad4 NFE exome AF: 0.0157

Gnomad4 OTH exome AF: 0.0126

GnomAD4 genome AF: 0.0110 AC: 1668 AN: 152076 Hom.: 16 Cov.: 33 AF XY: 0.0106 AC XY: 787 AN XY: 74332

Gnomad4 AFR AF: 0.00321

Gnomad4 AMR AF: 0.0112

Gnomad4 ASJ AF: 0.0190

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000622

Gnomad4 FIN AF: 0.0119

Gnomad4 NFE AF: 0.0167

Gnomad4 OTH AF: 0.0128

Alfa AF: 0.00572 Hom.: 2

Bravo AF: 0.0107

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Leukocyte adhesion deficiency 1 Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Apr 27, 2017

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to rule this variant out of causing disease. Therefore, this variant is classified as benign. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.69
DANN	Benign	0.50

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: rs117989670; hg19: chr21-46305913;