dbSNP rs3828913: MICB:c.-27+3023C>A (chr6-31498018-C-A) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_001289160.2(MICB):c.-27+3023C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00796 in 381,542 control chromosomes in the GnomAD database, including 134 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 0.0097 ( 71 hom., cov: 33)

Exomes 𝑓: 0.0068 ( 63 hom. )

Consequence

MICB
NM_001289160.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.02

Publications

9 publications found

Variant links:

Genes affected

MICB (HGNC:7091): (MHC class I polypeptide-related sequence B) This gene encodes a heavily glycosylated protein which is a ligand for the NKG2D type II receptor. Binding of the ligand activates the cytolytic response of natural killer (NK) cells, CD8 alphabeta T cells, and gammadelta T cells which express the receptor. This protein is stress-induced and is similar to MHC class I molecules; however, it does not associate with beta-2-microglobulin or bind peptides. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2014]

MICB 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=-0.8).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.148 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
MICB	NM_001289160.2 link	c.-27+3023C>A	intron_variant	Intron 1 of 5		NP_001276089.1	Q29980F5H7Q8B7Z8M1B4DUT9
MICB	NM_005931.5 link	c.-176C>A	upstream_gene_variant		ENST00000252229.7	NP_005922.2	Q29980-1A0A7D9H7X8
MICB	NM_001289161.2 link	c.-176C>A	upstream_gene_variant			NP_001276090.1	Q29980-2A0A0G2JHB5

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
MICB	ENST00000538442.5 link	c.-27+3023C>A	intron_variant	Intron 1 of 5	2		ENSP00000442345.1	F5H7Q8
MICB	ENST00000252229.7 link	c.-176C>A	upstream_gene_variant		1	NM_005931.5	ENSP00000252229.6	Q29980-1
MICB	ENST00000399150.7 link	c.-176C>A	upstream_gene_variant		1		ENSP00000382103.3	Q29980-2

Frequencies

GnomAD3 genomes

AF:

0.00977

AC:

1479

AN:

151430

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000926

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0258

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.157

Gnomad SAS

AF:

0.000831

Gnomad FIN

AF:

0.00284

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00274

Gnomad OTH

AF:

0.00865

GnomAD4 exome

AF:

0.00679

AC:

1562

AN:

229994

Hom.:

AF XY:

0.00595

AC XY:

743

AN XY:

124956

show subpopulations

African (AFR)

AF:

0.000296

AC:

AN:

3380

American (AMR)

AF:

0.0304

AC:

171

AN:

5622

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

5394

East Asian (EAS)

AF:

0.117

AC:

868

AN:

7450

South Asian (SAS)

AF:

0.000512

AC:

AN:

35158

European-Finnish (FIN)

AF:

0.00354

AC:

AN:

17808

Middle Eastern (MID)

AF:

0.000644

AC:

AN:

1554

European-Non Finnish (NFE)

AF:

0.00245

AC:

348

AN:

142212

Other (OTH)

AF:

0.00806

AC:

AN:

11416

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

136

203

271

339

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:

0.00974

AC:

1476

AN:

151548

Hom.:

Cov.:

AF XY:

0.0104

AC XY:

769

AN XY:

74076

show subpopulations

African (AFR)

AF:

0.000923

AC:

AN:

41150

American (AMR)

AF:

0.0257

AC:

392

AN:

15250

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3464

East Asian (EAS)

AF:

0.157

AC:

808

AN:

5152

South Asian (SAS)

AF:

0.000832

AC:

AN:

4808

European-Finnish (FIN)

AF:

0.00284

AC:

AN:

10552

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00274

AC:

186

AN:

67862

Other (OTH)

AF:

0.00856

AC:

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

151

226

302

377

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

<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:

0.00727

Hom.:

Bravo

AF:

0.0118

Asia WGS

AF:

0.0310

AC:

106

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

4.3

(source)

DANN

Benign

0.42

PhyloP100

-1.0

PromoterAI

-0.059

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