Genetic Variant MICB:c.-27+3047C>T (chr6-31498042-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_001289160.2(MICB):c.-27+3047C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.34 in 439,470 control chromosomes in the GnomAD database, including 25,412 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 0.38 ( 8453 hom., cov: 32)

Exomes 𝑓: 0.32 ( 16959 hom. )

Consequence

MICB
NM_001289160.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.269

Publications

35 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 = 0.488 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+3047C>T	intron	N/A	NP_001276089.1
MICB	NM_005931.5	MANE Select	c.-152C>T	upstream_gene	N/A	NP_005922.2
MICB	NM_001289161.2		c.-152C>T	upstream_gene	N/A	NP_001276090.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
MICB	ENST00000538442.5	TSL:2	c.-27+3047C>T	intron	N/A	ENSP00000442345.1
MICB	ENST00000252229.7	TSL:1 MANE Select	c.-152C>T	upstream_gene	N/A	ENSP00000252229.6
MICB	ENST00000399150.7	TSL:1	c.-152C>T	upstream_gene	N/A	ENSP00000382103.3

Frequencies

GnomAD3 genomes

AF:

0.383

AC:

50211

AN:

131142

Hom.:

8442

Cov.:

show subpopulations

Gnomad AFR

AF:

0.412

Gnomad AMI

AF:

0.333

Gnomad AMR

AF:

0.406

Gnomad ASJ

AF:

0.409

Gnomad EAS

AF:

0.505

Gnomad SAS

AF:

0.440

Gnomad FIN

AF:

0.342

Gnomad MID

AF:

0.368

Gnomad NFE

AF:

0.353

Gnomad OTH

AF:

0.392

GnomAD4 exome

AF:

0.322

AC:

99142

AN:

308224

Hom.:

16959

Cov.:

AF XY:

0.325

AC XY:

53556

AN XY:

164636

show subpopulations

African (AFR)

AF:

0.309

AC:

1540

AN:

4986

American (AMR)

AF:

0.360

AC:

2768

AN:

7692

Ashkenazi Jewish (ASJ)

AF:

0.332

AC:

2259

AN:

6810

East Asian (EAS)

AF:

0.498

AC:

4669

AN:

9372

South Asian (SAS)

AF:

0.368

AC:

14714

AN:

39962

European-Finnish (FIN)

AF:

0.304

AC:

7083

AN:

23312

Middle Eastern (MID)

AF:

0.413

AC:

994

AN:

2406

European-Non Finnish (NFE)

AF:

0.303

AC:

60302

AN:

198992

Other (OTH)

AF:

0.328

AC:

4813

AN:

14692

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

3101

6203

9304

12406

15507

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

898

1796

2694

3592

4490

<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:

0.383

AC:

50252

AN:

131246

Hom.:

8453

Cov.:

AF XY:

0.384

AC XY:

24754

AN XY:

64424

show subpopulations

African (AFR)

AF:

0.412

AC:

13709

AN:

33236

American (AMR)

AF:

0.406

AC:

5737

AN:

14138

Ashkenazi Jewish (ASJ)

AF:

0.409

AC:

1191

AN:

2910

East Asian (EAS)

AF:

0.505

AC:

2389

AN:

4730

South Asian (SAS)

AF:

0.439

AC:

1894

AN:

4312

European-Finnish (FIN)

AF:

0.342

AC:

3254

AN:

9520

Middle Eastern (MID)

AF:

0.361

AC:

AN:

252

European-Non Finnish (NFE)

AF:

0.353

AC:

20985

AN:

59466

Other (OTH)

AF:

0.392

AC:

723

AN:

1844

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1747

3493

5240

6986

8733

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

500

1000

1500

2000

2500

<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:

0.313

Hom.:

21852

Bravo

AF:

0.333

Asia WGS

AF:

0.378

AC:

1298

AN:

3436

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

7.7

(source)

DANN

Benign

0.56

PhyloP100

0.27

PromoterAI

-0.23

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