Variant 6-31498259-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7

The NM_005931.5(MICB):c.66C>T(p.Ala22=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000765 in 1,569,418 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000073 ( 1 hom. )

Consequence

MICB
NM_005931.5 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -3.57

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 made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.6).

BP6

Variant 6-31498259-C-T is Benign according to our data. Variant chr6-31498259-C-T is described in ClinVar as [Benign]. Clinvar id is 726697.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-3.57 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
MICB	NM_005931.5 linkuse as main transcript	c.66C>T	p.Ala22=	synonymous_variant	1/6	ENST00000252229.7
MICB	NM_001289161.2 linkuse as main transcript	c.66C>T	p.Ala22=	synonymous_variant	1/6
MICB	NM_001289160.2 linkuse as main transcript	c.-27+3264C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MICB	ENST00000252229.7 linkuse as main transcript	c.66C>T	p.Ala22=	synonymous_variant	1/6	1	NM_005931.5	P1	Q29980-1
MICB	ENST00000399150.7 linkuse as main transcript	c.66C>T	p.Ala22=	synonymous_variant	1/6	1			Q29980-2
MICB	ENST00000538442.5 linkuse as main transcript	c.-27+3264C>T		intron_variant		2

Frequencies

GnomAD3 genomes

AF:

0.000105

AC:

AN:

152094

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00105

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000428

AC:

AN:

212668

Hom.:

AF XY:

0.000317

AC XY:

AN XY:

116870

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00280

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000107

Gnomad OTH exome

AF:

0.000191

GnomAD4 exome

AF:

0.0000734

AC:

104

AN:

1417324

Hom.:

Cov.:

AF XY:

0.0000553

AC XY:

AN XY:

704866

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00241

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000184

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.000105

AC:

AN:

152094

Hom.:

Cov.:

AF XY:

0.0000942

AC XY:

AN XY:

74302

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00105

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000331

Hom.:

Bravo

AF:

0.000196

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 09, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.60

Cadd

Benign

5.8

Dann

Benign

0.79

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over