Genetic Variant ITGB2:c.-4+95A>G (chr21-44920726-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000211.5(ITGB2):c.-4+95A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.568 in 152,268 control chromosomes in the GnomAD database, including 27,373 homozygotes. 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: 𝑓 0.57 ( 27362 hom., cov: 33)

Exomes 𝑓: 0.44 ( 11 hom. )

Consequence

ITGB2
NM_000211.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.04

Publications

3 publications found

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]

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

ITGB2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.864 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
ITGB2	NM_000211.5 link	c.-4+95A>G	intron_variant	Intron 1 of 15	ENST00000652462.1	NP_000202.3	P05107A0A494C0X7
ITGB2	NM_001127491.3 link	c.-4+7928A>G	intron_variant	Intron 1 of 15		NP_001120963.2	P05107A0A494C0X7
ITGB2	NM_001303238.2 link	c.-254+95A>G	intron_variant	Intron 1 of 15		NP_001290167.1	P05107B4E0R1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITGB2	ENST00000652462.1 link	c.-4+95A>G		intron_variant	Intron 1 of 15		NM_000211.5	ENSP00000498780.1		A0A494C0X7

Frequencies

GnomAD3 genomes

AF:

0.568

AC:

86278

AN:

152026

Hom.:

27294

Cov.:

show subpopulations

Gnomad AFR

AF:

0.871

Gnomad AMI

AF:

0.487

Gnomad AMR

AF:

0.513

Gnomad ASJ

AF:

0.497

Gnomad EAS

AF:

0.434

Gnomad SAS

AF:

0.389

Gnomad FIN

AF:

0.442

Gnomad MID

AF:

0.592

Gnomad NFE

AF:

0.443

Gnomad OTH

AF:

0.537

GnomAD4 exome

AF:

0.444

AC:

AN:

124

Hom.:

AF XY:

0.476

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

1.00

AC:

AN:

American (AMR)

AF:

0.500

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.500

AC:

AN:

South Asian (SAS)

AF:

0.333

AC:

AN:

European-Finnish (FIN)

AF:

0.500

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.418

AC:

AN:

Other (OTH)

AF:

0.500

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.568

AC:

86414

AN:

152144

Hom.:

27362

Cov.:

AF XY:

0.564

AC XY:

41967

AN XY:

74384

show subpopulations

African (AFR)

AF:

0.871

AC:

36167

AN:

41520

American (AMR)

AF:

0.513

AC:

7848

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.497

AC:

1724

AN:

3470

East Asian (EAS)

AF:

0.436

AC:

2257

AN:

5174

South Asian (SAS)

AF:

0.389

AC:

1876

AN:

4826

European-Finnish (FIN)

AF:

0.442

AC:

4673

AN:

10578

Middle Eastern (MID)

AF:

0.605

AC:

178

AN:

294

European-Non Finnish (NFE)

AF:

0.443

AC:

30110

AN:

67960

Other (OTH)

AF:

0.538

AC:

1137

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

1736

3473

5209

6946

8682

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

694

1388

2082

2776

3470

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.510

Hom.:

2751

Bravo

AF:

0.591

Asia WGS

AF:

0.453

AC:

1579

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.92

(source)

DANN

Benign

0.45

PhyloP100

-1.0

PromoterAI

-0.0086

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over