Genetic Variant NM_005931.5: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:

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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=-0.91).

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

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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