Genetic Variant ITGB2-AS1:n.232T>C (chr21-44921282-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_001127491.3(ITGB2):c.-4+7372A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.227 in 152,208 control chromosomes in the GnomAD database, including 4,073 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 0.23 ( 4070 hom., cov: 32)

Exomes 𝑓: 0.17 ( 3 hom. )

Consequence

ITGB2
NM_001127491.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -3.27

Publications

15 publications found

Variant links:

Genes affected

ITGB2-AS1 (HGNC:44304): (ITGB2 antisense RNA 1)

ITGB2-AS1 links:

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=-0.86).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.293 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001127491.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	HGVSc	Effect	Exon Rank	Protein	UniProt
ITGB2	NM_001127491.3	c.-4+7372A>G	intron	N/A	NP_001120963.2	P05107
ITGB2-AS1	NR_038311.1	n.248T>C	non_coding_transcript_exon	Exon 1 of 5
ITGB2-AS1	NR_038312.1	n.248T>C	non_coding_transcript_exon	Exon 1 of 4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ITGB2-AS1	ENST00000441379.5	TSL:1	n.232T>C	non_coding_transcript_exon	Exon 1 of 4
ITGB2	ENST00000355153.8	TSL:2	c.-4+7372A>G	intron	N/A	ENSP00000347279.4	P05107
ITGB2	ENST00000397850.6	TSL:5	c.-233-232A>G	intron	N/A	ENSP00000380948.2	P05107

Frequencies

GnomAD3 genomes

AF:

0.227

AC:

34461

AN:

151924

Hom.:

4058

Cov.:

show subpopulations

Gnomad AFR

AF:

0.201

Gnomad AMI

AF:

0.309

Gnomad AMR

AF:

0.299

Gnomad ASJ

AF:

0.266

Gnomad EAS

AF:

0.105

Gnomad SAS

AF:

0.306

Gnomad FIN

AF:

0.175

Gnomad MID

AF:

0.313

Gnomad NFE

AF:

0.234

Gnomad OTH

AF:

0.232

GnomAD4 exome

AF:

0.169

AC:

AN:

166

Hom.:

Cov.:

AF XY:

0.190

AC XY:

AN XY:

116

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AF:

0.500

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AF:

0.300

AC:

AN:

European-Finnish (FIN)

AF:

0.167

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.151

AC:

AN:

106

Other (OTH)

AF:

0.208

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

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:

0.227

AC:

34512

AN:

152042

Hom.:

4070

Cov.:

AF XY:

0.227

AC XY:

16840

AN XY:

74332

show subpopulations

African (AFR)

AF:

0.202

AC:

8352

AN:

41444

American (AMR)

AF:

0.299

AC:

4563

AN:

15236

Ashkenazi Jewish (ASJ)

AF:

0.266

AC:

922

AN:

3470

East Asian (EAS)

AF:

0.105

AC:

546

AN:

5184

South Asian (SAS)

AF:

0.306

AC:

1478

AN:

4830

European-Finnish (FIN)

AF:

0.175

AC:

1851

AN:

10598

Middle Eastern (MID)

AF:

0.310

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.234

AC:

15934

AN:

67972

Other (OTH)

AF:

0.235

AC:

494

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1370

2740

4110

5480

6850

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

372

744

1116

1488

1860

<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:

0.229

Hom.:

6777

Bravo

AF:

0.235

Asia WGS

AF:

0.214

AC:

745

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.44

(source)

DANN

Benign

0.42

PhyloP100

-3.3

PromoterAI

-0.052

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