Genetic Variant MICB:c.*1300C>T (chr6-31511209-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_005931.5(MICB):c.*1300C>T variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.314 in 152,110 control chromosomes in the GnomAD database, including 7,752 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 0.31 ( 7752 hom., cov: 33)

Exomes 𝑓: 0.38 ( 0 hom. )

Consequence

MICB
NM_005931.5 downstream_gene

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.788

Publications

44 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:

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 (AFR) allele frequency at 95% confidence interval = 0.367 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
MICB	NM_005931.5 link	c.*1300C>T	downstream_gene_variant	ENST00000252229.7	NP_005922.2	Q29980-1A0A7D9H7X8
MICB	NM_001289160.2 link	c.*1300C>T	downstream_gene_variant		NP_001276089.1	Q29980F5H7Q8B7Z8M1B4DUT9
MICB	NM_001289161.2 link	c.*1300C>T	downstream_gene_variant		NP_001276090.1	Q29980-2A0A0G2JHB5

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
MICB	ENST00000252229.7 link	c.*1300C>T	downstream_gene_variant	1	NM_005931.5	ENSP00000252229.6	Q29980-1
MICB	ENST00000399150.7 link	c.*1300C>T	downstream_gene_variant	1		ENSP00000382103.3	Q29980-2
MICB	ENST00000538442.5 link	c.*1300C>T	downstream_gene_variant	2		ENSP00000442345.1	F5H7Q8

Frequencies

GnomAD3 genomes

AF:

0.314

AC:

47755

AN:

151984

Hom.:

7743

Cov.:

show subpopulations

Gnomad AFR

AF:

0.372

Gnomad AMI

AF:

0.260

Gnomad AMR

AF:

0.208

Gnomad ASJ

AF:

0.367

Gnomad EAS

AF:

0.266

Gnomad SAS

AF:

0.298

Gnomad FIN

AF:

0.283

Gnomad MID

AF:

0.373

Gnomad NFE

AF:

0.311

Gnomad OTH

AF:

0.300

GnomAD4 exome

AF:

0.375

AC:

AN:

Hom.:

AF XY:

0.333

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.500

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.500

AC:

AN:

Other (OTH)

AF:

0.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.314

AC:

47797

AN:

152102

Hom.:

7752

Cov.:

AF XY:

0.309

AC XY:

22996

AN XY:

74342

show subpopulations

African (AFR)

AF:

0.372

AC:

15418

AN:

41478

American (AMR)

AF:

0.208

AC:

3188

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.367

AC:

1272

AN:

3466

East Asian (EAS)

AF:

0.266

AC:

1379

AN:

5180

South Asian (SAS)

AF:

0.299

AC:

1439

AN:

4820

European-Finnish (FIN)

AF:

0.283

AC:

2994

AN:

10570

Middle Eastern (MID)

AF:

0.384

AC:

113

AN:

294

European-Non Finnish (NFE)

AF:

0.311

AC:

21127

AN:

67974

Other (OTH)

AF:

0.298

AC:

630

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1725

3451

5176

6902

8627

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

480

960

1440

1920

2400

<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:

0.316

Hom.:

28123

Bravo

AF:

0.313

Asia WGS

AF:

0.303

AC:

1055

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

3.6

(source)

DANN

Benign

0.47

PhyloP100

0.79

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over