dbSNP rs760456: ITGB2:c.147+784C>G (chr21-44909500-G-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.147+784C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.642 in 152,150 control chromosomes in the GnomAD database, including 31,656 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 0.64 ( 31623 hom., cov: 32)

Exomes 𝑓: 0.60 ( 33 hom. )

Consequence

ITGB2
NM_000211.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0770

Publications

11 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:

LOC107987303 (HGNC:):

LOC107987303 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=-0.91).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.698 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.147+784C>G	intron	N/A	NP_000202.3	P05107
ITGB2	NM_001127491.3		c.147+784C>G	intron	N/A	NP_001120963.2	P05107
ITGB2	NM_001303238.2		c.-61+784C>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.147+784C>G	intron	N/A	ENSP00000498780.1	A0A494C0X7
ITGB2	ENST00000302347.10	TSL:1	c.147+784C>G	intron	N/A	ENSP00000303242.6	A0AAA9WZN5
ITGB2	ENST00000397852.5	TSL:1	c.147+784C>G	intron	N/A	ENSP00000380950.1	P05107

Frequencies

GnomAD3 genomes

AF:

0.642

AC:

97567

AN:

151878

Hom.:

31598

Cov.:

show subpopulations

Gnomad AFR

AF:

0.599

Gnomad AMI

AF:

0.768

Gnomad AMR

AF:

0.702

Gnomad ASJ

AF:

0.757

Gnomad EAS

AF:

0.570

Gnomad SAS

AF:

0.720

Gnomad FIN

AF:

0.508

Gnomad MID

AF:

0.739

Gnomad NFE

AF:

0.667

Gnomad OTH

AF:

0.684

GnomAD4 exome

AF:

0.604

AC:

AN:

154

Hom.:

Cov.:

AF XY:

0.625

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.250

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

1.00

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AF:

0.786

AC:

AN:

European-Finnish (FIN)

AF:

0.484

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.694

AC:

AN:

Other (OTH)

AF:

0.750

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

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:

0.642

AC:

97638

AN:

151996

Hom.:

31623

Cov.:

AF XY:

0.639

AC XY:

47480

AN XY:

74296

show subpopulations

African (AFR)

AF:

0.599

AC:

24806

AN:

41442

American (AMR)

AF:

0.703

AC:

10723

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.757

AC:

2627

AN:

3472

East Asian (EAS)

AF:

0.570

AC:

2942

AN:

5160

South Asian (SAS)

AF:

0.718

AC:

3460

AN:

4816

European-Finnish (FIN)

AF:

0.508

AC:

5357

AN:

10550

Middle Eastern (MID)

AF:

0.740

AC:

216

AN:

292

European-Non Finnish (NFE)

AF:

0.667

AC:

45370

AN:

67982

Other (OTH)

AF:

0.682

AC:

1437

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1783

3566

5349

7132

8915

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

790

1580

2370

3160

3950

<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:

0.550

Hom.:

1668

Bravo

AF:

0.650

Asia WGS

AF:

0.652

AC:

2268

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

2.8

(source)

DANN

Benign

0.44

PhyloP100

-0.077

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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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