Genetic Variant MICB:c.613+73G>A (chr6-31506503-G-A) – 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.613+73G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.118 in 1,510,080 control chromosomes in the GnomAD database, including 10,845 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 0.12 ( 1153 hom., cov: 32)

Exomes 𝑓: 0.12 ( 9692 hom. )

Consequence

MICB
NM_005931.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.26

Publications

18 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:

Genome browser will be placed here

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=-1.0).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.143 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
MICB	NM_005931.5 link	c.613+73G>A	intron_variant	Intron 3 of 5	ENST00000252229.7	NP_005922.2	Q29980-1A0A7D9H7X8
MICB	NM_001289160.2 link	c.517+73G>A	intron_variant	Intron 3 of 5		NP_001276089.1	Q29980F5H7Q8B7Z8M1B4DUT9
MICB	NM_001289161.2 link	c.484+73G>A	intron_variant	Intron 3 of 5		NP_001276090.1	Q29980-2A0A0G2JHB5

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
MICB	ENST00000252229.7 link	c.613+73G>A	intron_variant	Intron 3 of 5	1	NM_005931.5	ENSP00000252229.6	Q29980-1
MICB	ENST00000399150.7 link	c.484+73G>A	intron_variant	Intron 3 of 5	1		ENSP00000382103.3	Q29980-2
MICB	ENST00000538442.5 link	c.517+73G>A	intron_variant	Intron 3 of 5	2		ENSP00000442345.1	F5H7Q8
MICB	ENST00000494577.1 link	n.496+73G>A	intron_variant	Intron 1 of 2	3

Frequencies

GnomAD3 genomes

AF:

0.120

AC:

18237

AN:

152098

Hom.:

1152

Cov.:

show subpopulations

Gnomad AFR

AF:

0.132

Gnomad AMI

AF:

0.0208

Gnomad AMR

AF:

0.0858

Gnomad ASJ

AF:

0.0493

Gnomad EAS

AF:

0.131

Gnomad SAS

AF:

0.153

Gnomad FIN

AF:

0.149

Gnomad MID

AF:

0.130

Gnomad NFE

AF:

0.117

Gnomad OTH

AF:

0.119

GnomAD4 exome

AF:

0.118

AC:

160086

AN:

1357864

Hom.:

9692

AF XY:

0.119

AC XY:

79723

AN XY:

671802

show subpopulations

African (AFR)

AF:

0.131

AC:

4018

AN:

30564

American (AMR)

AF:

0.0778

AC:

2761

AN:

35500

Ashkenazi Jewish (ASJ)

AF:

0.0537

AC:

1170

AN:

21800

East Asian (EAS)

AF:

0.134

AC:

5116

AN:

38234

South Asian (SAS)

AF:

0.145

AC:

10745

AN:

74150

European-Finnish (FIN)

AF:

0.151

AC:

7234

AN:

48028

Middle Eastern (MID)

AF:

0.0950

AC:

514

AN:

5408

European-Non Finnish (NFE)

AF:

0.117

AC:

122167

AN:

1047838

Other (OTH)

AF:

0.113

AC:

6361

AN:

56342

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

7159

14318

21476

28635

35794

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4524

9048

13572

18096

22620

<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:

0.120

AC:

18254

AN:

152216

Hom.:

1153

Cov.:

AF XY:

0.120

AC XY:

8966

AN XY:

74426

show subpopulations

African (AFR)

AF:

0.132

AC:

5479

AN:

41534

American (AMR)

AF:

0.0863

AC:

1320

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.0493

AC:

171

AN:

3468

East Asian (EAS)

AF:

0.132

AC:

681

AN:

5174

South Asian (SAS)

AF:

0.153

AC:

736

AN:

4822

European-Finnish (FIN)

AF:

0.149

AC:

1582

AN:

10610

Middle Eastern (MID)

AF:

0.126

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.117

AC:

7979

AN:

67992

Other (OTH)

AF:

0.118

AC:

250

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

825

1650

2474

3299

4124

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

216

432

648

864

1080

<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:

0.109

Hom.:

1078

Bravo

AF:

0.116

Asia WGS

AF:

0.145

AC:

507

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.46

(source)

DANN

Benign

0.67

PhyloP100

-2.3

Mutation Taster

=100/0

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over