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GeneBe

rs61747615

Positions:

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 2P and 9B. PM2BP4_ModerateBP6_ModerateBP7BS1

The NM_000211.5(ITGB2):​c.1497G>A​(p.Lys499=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000327 in 1,613,466 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0017 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00018 ( 0 hom. )

Consequence

ITGB2
NM_000211.5 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.428
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -7 ACMG points.

PM2
?
    PM2 - Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
Very rare variant in population databases, with high coverage;
BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.4).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 21-44890138-C-T is Benign according to our data. Variant chr21-44890138-C-T is described in ClinVar as [Benign]. Clinvar id is 461471.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr21-44890138-C-T is described in Lovd as [Benign].
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=0.428 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00173 (264/152278) while in subpopulation AFR AF= 0.00601 (250/41568). AF 95% confidence interval is 0.0054. There are 0 homozygotes in gnomad4. There are 119 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ITGB2NM_000211.5 linkuse as main transcriptc.1497G>A p.Lys499= synonymous_variant 12/16 ENST00000652462.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ITGB2ENST00000652462.1 linkuse as main transcriptc.1497G>A p.Lys499= synonymous_variant 12/16 NM_000211.5 P1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00174
AC:
265
AN:
152160
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00606
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000851
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.000479
GnomAD3 exomes
AF:
0.000442
AC:
111
AN:
250928
Hom.:
0
AF XY:
0.000324
AC XY:
44
AN XY:
135792
show subpopulations
Gnomad AFR exome
AF:
0.00625
Gnomad AMR exome
AF:
0.000231
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.000326
GnomAD4 exome
AF:
0.000180
AC:
263
AN:
1461188
Hom.:
0
Cov.:
33
AF XY:
0.000168
AC XY:
122
AN XY:
726914
show subpopulations
Gnomad4 AFR exome
AF:
0.00675
Gnomad4 AMR exome
AF:
0.000224
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000696
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000270
Gnomad4 OTH exome
AF:
0.000265
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00173
AC:
264
AN:
152278
Hom.:
0
Cov.:
33
AF XY:
0.00160
AC XY:
119
AN XY:
74450
show subpopulations
Gnomad4 AFR
AF:
0.00601
Gnomad4 AMR
AF:
0.000850
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.000474
Alfa
AF:
0.00103
Hom.:
0
Bravo
AF:
0.00200
Asia WGS
AF:
0.000289
AC:
1
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Leukocyte adhesion deficiency 1 Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeJan 31, 2024- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.40
CADD
Benign
7.2
DANN
Benign
0.66

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.030
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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs61747615; hg19: chr21-46310053; API