NM_000211.5:c.148-1089A>G

Variant names:

• chr21-44908184-T-C
• rs760462
• NM_000211.5:c.148-1089A>G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000211.5(ITGB2):​c.148-1089A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.847 in 719,108 control chromosomes in the GnomAD database, including 259,384 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.87 (58166 hom., cov: 31)
  • Exomes 𝑓: 0.84 (201218 hom.)
• Consequence: ITGB2 NM_000211.5 intron
• Scores: Splicing: ADA: 0.00002529
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -3.48

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]

LOC107987303 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_addAF=-0.906843).
• BP6: Variant 21-44908184-T-C is Benign according to our data. Variant chr21-44908184-T-C is described in ClinVar as [Benign]. Clinvar id is 803634.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-44908184-T-C is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.959 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITGB2	NM_000211.5	c.148-1089A>G		intron_variant	Intron 3 of 15	ENST00000652462.1	NP_000202.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITGB2	ENST00000652462.1	c.148-1089A>G		intron_variant	Intron 3 of 15		NM_000211.5	ENSP00000498780.1

Frequencies

GnomAD3 genomes AF: 0.872 AC: 132527 AN: 152022 Hom.: 58100 Cov.: 31

Gnomad AFR AF: 0.967

Gnomad AMI AF: 0.787

Gnomad AMR AF: 0.894

Gnomad ASJ AF: 0.863

Gnomad EAS AF: 0.773

Gnomad SAS AF: 0.921

Gnomad FIN AF: 0.798

Gnomad MID AF: 0.839

Gnomad NFE AF: 0.826

Gnomad OTH AF: 0.863

GnomAD3 exomes AF: 0.851 AC: 157890 AN: 185526 Hom.: 67506 AF XY: 0.850 AC XY: 87151 AN XY: 102482

Gnomad AFR exome AF: 0.970

Gnomad AMR exome AF: 0.928

Gnomad ASJ exome AF: 0.859

Gnomad EAS exome AF: 0.764

Gnomad SAS exome AF: 0.910

Gnomad FIN exome AF: 0.786

Gnomad NFE exome AF: 0.823

Gnomad OTH exome AF: 0.850

GnomAD4 exome AF: 0.841 AC: 476683 AN: 566968 Hom.: 201218 Cov.: 0 AF XY: 0.844 AC XY: 258338 AN XY: 306226

Gnomad4 AFR exome AF: 0.967

Gnomad4 AMR exome AF: 0.923

Gnomad4 ASJ exome AF: 0.863

Gnomad4 EAS exome AF: 0.756

Gnomad4 SAS exome AF: 0.910

Gnomad4 FIN exome AF: 0.796

Gnomad4 NFE exome AF: 0.825

Gnomad4 OTH exome AF: 0.846

GnomAD4 genome AF: 0.872 AC: 132651 AN: 152140 Hom.: 58166 Cov.: 31 AF XY: 0.872 AC XY: 64848 AN XY: 74360

Gnomad4 AFR AF: 0.967

Gnomad4 AMR AF: 0.895

Gnomad4 ASJ AF: 0.863

Gnomad4 EAS AF: 0.773

Gnomad4 SAS AF: 0.921

Gnomad4 FIN AF: 0.798

Gnomad4 NFE AF: 0.826

Gnomad4 OTH AF: 0.861

Alfa AF: 0.839 Hom.: 80445

Bravo AF: 0.879

TwinsUK AF: 0.819 AC: 3038

ALSPAC AF: 0.819 AC: 3156

ESP6500AA AF: 0.975 AC: 1666

ESP6500EA AF: 0.831 AC: 3260

ExAC AF: 0.831 AC: 91552

Asia WGS AF: 0.879 AC: 3058 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Jan 24, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 99% of patients studied by a panel of primary immunodeficiencies. Number of patients: 94. Only high quality variants are reported. -

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Leukocyte adhesion deficiency 1 Benign:1

May 28, 2019

Mendelics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.91	T
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.54
DANN	Benign	0.31
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.0012	N
GERP RS		-2.3

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000025
dbscSNV1_RF	Benign	0.0
SpliceAI score (max)		0.010		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: rs760462; hg19: chr21-46328099;