Genetic Variant MICB:c.-54G>T (chr6-31498140-G-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000399150.7(MICB):c.-54G>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0378 in 1,472,538 control chromosomes in the GnomAD database, including 1,346 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 0.033 ( 90 hom., cov: 31)

Exomes 𝑓: 0.038 ( 1256 hom. )

Consequence

MICB
ENST00000399150.7 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.454

Publications

21 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=-0.77).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0528 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000399150.7. 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+3145G>T	intron	N/A	NP_001276089.1
MICB	NM_005931.5	MANE Select	c.-54G>T	upstream_gene	N/A	NP_005922.2
MICB	NM_001289161.2		c.-54G>T	upstream_gene	N/A	NP_001276090.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
MICB	ENST00000399150.7	TSL:1	c.-54G>T	5_prime_UTR	Exon 1 of 6	ENSP00000382103.3
MICB	ENST00000538442.5	TSL:2	c.-27+3145G>T	intron	N/A	ENSP00000442345.1
MICB	ENST00000252229.7	TSL:1 MANE Select	c.-54G>T	upstream_gene	N/A	ENSP00000252229.6

Frequencies

GnomAD3 genomes

AF:

0.0335

AC:

5090

AN:

152164

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0249

Gnomad AMI

AF:

0.152

Gnomad AMR

AF:

0.0315

Gnomad ASJ

AF:

0.0473

Gnomad EAS

AF:

0.0278

Gnomad SAS

AF:

0.0592

Gnomad FIN

AF:

0.0124

Gnomad MID

AF:

0.0285

Gnomad NFE

AF:

0.0386

Gnomad OTH

AF:

0.0354

GnomAD4 exome

AF:

0.0383

AC:

50595

AN:

1320256

Hom.:

1256

Cov.:

AF XY:

0.0387

AC XY:

25420

AN XY:

657500

show subpopulations

African (AFR)

AF:

0.0230

AC:

661

AN:

28780

American (AMR)

AF:

0.0316

AC:

1187

AN:

37618

Ashkenazi Jewish (ASJ)

AF:

0.0488

AC:

1094

AN:

22424

East Asian (EAS)

AF:

0.0226

AC:

680

AN:

30138

South Asian (SAS)

AF:

0.0550

AC:

4372

AN:

79456

European-Finnish (FIN)

AF:

0.0138

AC:

682

AN:

49380

Middle Eastern (MID)

AF:

0.0266

AC:

142

AN:

5332

European-Non Finnish (NFE)

AF:

0.0391

AC:

39632

AN:

1013904

Other (OTH)

AF:

0.0403

AC:

2145

AN:

53224

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

2154

4307

6461

8614

10768

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1572

3144

4716

6288

7860

<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:

0.0335

AC:

5101

AN:

152282

Hom.:

Cov.:

AF XY:

0.0335

AC XY:

2492

AN XY:

74460

show subpopulations

African (AFR)

AF:

0.0252

AC:

1047

AN:

41556

American (AMR)

AF:

0.0316

AC:

484

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.0473

AC:

164

AN:

3468

East Asian (EAS)

AF:

0.0278

AC:

144

AN:

5176

South Asian (SAS)

AF:

0.0584

AC:

282

AN:

4830

European-Finnish (FIN)

AF:

0.0124

AC:

132

AN:

10620

Middle Eastern (MID)

AF:

0.0306

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0386

AC:

2626

AN:

68018

Other (OTH)

AF:

0.0351

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

245

491

736

982

1227

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

124

186

248

310

<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:

0.0261

Hom.:

Bravo

AF:

0.0337

Asia WGS

AF:

0.0400

AC:

138

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

3.8

(source)

DANN

Benign

0.60

PhyloP100

0.45

PromoterAI

-0.026

Neutral

(source)

Mutation Taster

=300/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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