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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
MICB	NM_001289160.2 link	c.-27+3047C>T	intron_variant	Intron 1 of 5		NP_001276089.1	Q29980F5H7Q8B7Z8M1B4DUT9
MICB	NM_005931.5 link	c.-152C>T	upstream_gene_variant		ENST00000252229.7	NP_005922.2	Q29980-1A0A7D9H7X8
MICB	NM_001289161.2 link	c.-152C>T	upstream_gene_variant			NP_001276090.1	Q29980-2A0A0G2JHB5

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
MICB	ENST00000538442.5 link	c.-27+3047C>T	intron_variant	Intron 1 of 5	2		ENSP00000442345.1	F5H7Q8
MICB	ENST00000252229.7 link	c.-152C>T	upstream_gene_variant		1	NM_005931.5	ENSP00000252229.6	Q29980-1
MICB	ENST00000399150.7 link	c.-152C>T	upstream_gene_variant		1		ENSP00000382103.3	Q29980-2

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 v4.3

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over