Genetic Variant NM_001289160.2: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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001289160.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
MICB	NM_001289160.2		c.-27+3023C>A	intron	N/A	NP_001276089.1
MICB	NM_005931.5	MANE Select	c.-176C>A	upstream_gene	N/A	NP_005922.2
MICB	NM_001289161.2		c.-176C>A	upstream_gene	N/A	NP_001276090.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
MICB	ENST00000538442.5	TSL:2	c.-27+3023C>A	intron	N/A	ENSP00000442345.1
MICB	ENST00000252229.7	TSL:1 MANE Select	c.-176C>A	upstream_gene	N/A	ENSP00000252229.6
MICB	ENST00000399150.7	TSL:1	c.-176C>A	upstream_gene	N/A	ENSP00000382103.3

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 v4.9

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over