rs2855812

Variant names:

• chr6-31504943-G-T
• rs2855812
• NM_005931.5:c.71-674G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005931.5(MICB):​c.71-674G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.226 in 151,948 control chromosomes in the GnomAD database, including 4,033 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 0.23 (4033 hom., cov: 31)
• Consequence: MICB NM_005931.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.367
• Publications: 83 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.252 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MICB	NM_005931.5	c.71-674G>T		intron_variant	Intron 1 of 5	ENST00000252229.7	NP_005922.2
MICB	NM_001289160.2	c.-26-674G>T		intron_variant	Intron 1 of 5		NP_001276089.1
MICB	NM_001289161.2	c.71-674G>T		intron_variant	Intron 1 of 5		NP_001276090.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MICB	ENST00000252229.7	c.71-674G>T		intron_variant	Intron 1 of 5	1	NM_005931.5	ENSP00000252229.6
MICB	ENST00000399150.7	c.71-674G>T		intron_variant	Intron 1 of 5	1		ENSP00000382103.3
MICB	ENST00000538442.5	c.-26-674G>T		intron_variant	Intron 1 of 5	2		ENSP00000442345.1

Frequencies

GnomAD3 genomes AF: 0.226 AC: 34323 AN: 151830 Hom.: 4026 Cov.: 31

Gnomad AFR AF: 0.256

Gnomad AMI AF: 0.175

Gnomad AMR AF: 0.141

Gnomad ASJ AF: 0.112

Gnomad EAS AF: 0.203

Gnomad SAS AF: 0.199

Gnomad FIN AF: 0.231

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.237

Gnomad OTH AF: 0.206

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.226 AC: 34350 AN: 151948 Hom.: 4033 Cov.: 31 AF XY: 0.221 AC XY: 16440 AN XY: 74254

African (AFR) AF: 0.256 AC: 10580 AN: 41390

American (AMR) AF: 0.141 AC: 2162 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.112 AC: 387 AN: 3470

East Asian (EAS) AF: 0.203 AC: 1048 AN: 5160

South Asian (SAS) AF: 0.199 AC: 956 AN: 4814

European-Finnish (FIN) AF: 0.231 AC: 2433 AN: 10552

Middle Eastern (MID) AF: 0.180 AC: 53 AN: 294

European-Non Finnish (NFE) AF: 0.238 AC: 16141 AN: 67960

Other (OTH) AF: 0.204 AC: 430 AN: 2104

Alfa AF: 0.237 Hom.: 19489

Bravo AF: 0.222

Asia WGS AF: 0.207 AC: 722 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	3.9
DANN	Benign	0.52
PhyloP100		0.37
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2855812; hg19: chr6-31472720;