Genetic Variant NM_000211.5: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, Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae), Orphanet

ITGB2 links:

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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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000211.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ITGB2	NM_000211.5	MANE Select	c.-4+95A>G	intron	N/A	NP_000202.3	P05107
ITGB2	NM_001127491.3		c.-4+7928A>G	intron	N/A	NP_001120963.2	P05107
ITGB2	NM_001303238.2		c.-254+95A>G	intron	N/A	NP_001290167.1	B4E0R1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ITGB2	ENST00000652462.1	MANE Select	c.-4+95A>G	intron	N/A	ENSP00000498780.1	A0A494C0X7
ITGB2	ENST00000302347.10	TSL:1	c.-4+95A>G	intron	N/A	ENSP00000303242.6	A0AAA9WZN5
ITGB2	ENST00000397854.7	TSL:1	c.-4+95A>G	intron	N/A	ENSP00000380952.3	D3DSM0

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 v4.9

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over