rs3746972

chr21-44907920-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000211.5(ITGB2):c.148-825T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.166 in 591,072 control chromosomes in the GnomAD database, including 8,693 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.17 (2368 hom., cov: 33)
  • Exomes 𝑓: 0.16 (6325 hom.)
• Consequence: ITGB2 NM_000211.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.206

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=-0.84).
• BP6: Variant 21-44907920-A-G is Benign according to our data. Variant chr21-44907920-A-G is described in ClinVar as [Benign]. Clinvar id is 2688237.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.238 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ITGB2	NM_000211.5	c.148-825T>C		intron_variant		ENST00000652462.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ITGB2	ENST00000652462.1	c.148-825T>C		intron_variant			NM_000211.5	P1

Frequencies

GnomAD3 genomes AF: 0.170 AC: 25908 AN: 152170 Hom.: 2371 Cov.: 33

Gnomad AFR AF: 0.131

Gnomad AMI AF: 0.340

Gnomad AMR AF: 0.244

Gnomad ASJ AF: 0.184

Gnomad EAS AF: 0.135

Gnomad SAS AF: 0.0894

Gnomad FIN AF: 0.184

Gnomad MID AF: 0.153

Gnomad NFE AF: 0.181

Gnomad OTH AF: 0.167

GnomAD4 exome AF: 0.164 AC: 72060 AN: 438784 Hom.: 6325 AF XY: 0.160 AC XY: 37301 AN XY: 232866

Gnomad4 AFR exome AF: 0.127

Gnomad4 AMR exome AF: 0.250

Gnomad4 ASJ exome AF: 0.184

Gnomad4 EAS exome AF: 0.110

Gnomad4 SAS exome AF: 0.0939

Gnomad4 FIN exome AF: 0.176

Gnomad4 NFE exome AF: 0.175

Gnomad4 OTH exome AF: 0.172

GnomAD4 genome AF: 0.170 AC: 25913 AN: 152288 Hom.: 2368 Cov.: 33 AF XY: 0.171 AC XY: 12745 AN XY: 74470

Gnomad4 AFR AF: 0.131

Gnomad4 AMR AF: 0.245

Gnomad4 ASJ AF: 0.184

Gnomad4 EAS AF: 0.135

Gnomad4 SAS AF: 0.0889

Gnomad4 FIN AF: 0.184

Gnomad4 NFE AF: 0.181

Gnomad4 OTH AF: 0.166

Alfa AF: 0.180 Hom.: 3333

Bravo AF: 0.174

Asia WGS AF: 0.131 AC: 456 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Jan 24, 2024

This variant is classified as Benign based on local population frequency. This variant was detected in 32% of patients studied by a panel of primary immunodeficiencies. Number of patients: 30. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	0.64
Dann	Benign	0.68

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: rs3746972; hg19: chr21-46327835; COSMIC: COSV56608886; COSMIC: COSV56608886;