Genetic Variant NM_005931.5:c.71-108C>T (chr6-31505509-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.71-108C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.787 in 1,488,652 control chromosomes in the GnomAD database, including 463,851 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 0.80 ( 49327 hom., cov: 31)

Exomes 𝑓: 0.79 ( 414524 hom. )

Consequence

MICB
NM_005931.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.225

Publications

39 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=-0.99).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.888 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
MICB	NM_005931.5 link	c.71-108C>T	intron_variant	Intron 1 of 5	ENST00000252229.7	NP_005922.2	Q29980-1A0A7D9H7X8
MICB	NM_001289160.2 link	c.-26-108C>T	intron_variant	Intron 1 of 5		NP_001276089.1	Q29980F5H7Q8B7Z8M1B4DUT9
MICB	NM_001289161.2 link	c.71-108C>T	intron_variant	Intron 1 of 5		NP_001276090.1	Q29980-2A0A0G2JHB5

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
MICB	ENST00000252229.7 link	c.71-108C>T	intron_variant	Intron 1 of 5	1	NM_005931.5	ENSP00000252229.6	Q29980-1
MICB	ENST00000399150.7 link	c.71-108C>T	intron_variant	Intron 1 of 5	1		ENSP00000382103.3	Q29980-2
MICB	ENST00000538442.5 link	c.-26-108C>T	intron_variant	Intron 1 of 5	2		ENSP00000442345.1	F5H7Q8

Frequencies

GnomAD3 genomes

AF:

0.803

AC:

122051

AN:

152036

Hom.:

49274

Cov.:

show subpopulations

Gnomad AFR

AF:

0.835

Gnomad AMI

AF:

0.769

Gnomad AMR

AF:

0.844

Gnomad ASJ

AF:

0.946

Gnomad EAS

AF:

0.909

Gnomad SAS

AF:

0.893

Gnomad FIN

AF:

0.664

Gnomad MID

AF:

0.867

Gnomad NFE

AF:

0.773

Gnomad OTH

AF:

0.822

GnomAD4 exome

AF:

0.786

AC:

1050124

AN:

1336498

Hom.:

414524

AF XY:

0.790

AC XY:

520463

AN XY:

658870

show subpopulations

African (AFR)

AF:

0.840

AC:

25332

AN:

30174

American (AMR)

AF:

0.860

AC:

30050

AN:

34930

Ashkenazi Jewish (ASJ)

AF:

0.944

AC:

19871

AN:

21044

East Asian (EAS)

AF:

0.903

AC:

34930

AN:

38680

South Asian (SAS)

AF:

0.895

AC:

65462

AN:

73174

European-Finnish (FIN)

AF:

0.673

AC:

32096

AN:

47664

Middle Eastern (MID)

AF:

0.873

AC:

3254

AN:

3726

European-Non Finnish (NFE)

AF:

0.770

AC:

794898

AN:

1031772

Other (OTH)

AF:

0.799

AC:

44231

AN:

55334

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

10909

21818

32727

43636

54545

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

19360

38720

58080

77440

96800

<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:

0.803

AC:

122158

AN:

152154

Hom.:

49327

Cov.:

AF XY:

0.802

AC XY:

59635

AN XY:

74368

show subpopulations

African (AFR)

AF:

0.835

AC:

34681

AN:

41512

American (AMR)

AF:

0.844

AC:

12916

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.946

AC:

3282

AN:

3470

East Asian (EAS)

AF:

0.909

AC:

4709

AN:

5178

South Asian (SAS)

AF:

0.892

AC:

4309

AN:

4830

European-Finnish (FIN)

AF:

0.664

AC:

7019

AN:

10566

Middle Eastern (MID)

AF:

0.861

AC:

253

AN:

294

European-Non Finnish (NFE)

AF:

0.773

AC:

52551

AN:

67986

Other (OTH)

AF:

0.823

AC:

1737

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1239

2479

3718

4958

6197

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

876

1752

2628

3504

4380

<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:

0.794

Hom.:

203870

Bravo

AF:

0.817

Asia WGS

AF:

0.842

AC:

2927

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.99

CADD

Benign

0.70

(source)

DANN

Benign

0.67

PhyloP100

-0.23

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over