rs2855804

Variant names:

• chr6-31499588-C-T
• rs2855804
• NM_005931.5:c.70+1325C>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.70+1325C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.315 in 152,010 control chromosomes in the GnomAD database, including 7,769 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 0.31 (7769 hom., cov: 31)
• Consequence: MICB NM_005931.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.758
• Publications: 16 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.367 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MICB	NM_005931.5	c.70+1325C>T		intron_variant	Intron 1 of 5	ENST00000252229.7	NP_005922.2
MICB	NM_001289160.2	c.-27+4593C>T		intron_variant	Intron 1 of 5		NP_001276089.1
MICB	NM_001289161.2	c.70+1325C>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.70+1325C>T		intron_variant	Intron 1 of 5	1	NM_005931.5	ENSP00000252229.6
MICB	ENST00000399150.7	c.70+1325C>T		intron_variant	Intron 1 of 5	1		ENSP00000382103.3
MICB	ENST00000538442.5	c.-27+4593C>T		intron_variant	Intron 1 of 5	2		ENSP00000442345.1

Frequencies

GnomAD3 genomes AF: 0.315 AC: 47836 AN: 151892 Hom.: 7760 Cov.: 31

Gnomad AFR AF: 0.372

Gnomad AMI AF: 0.260

Gnomad AMR AF: 0.212

Gnomad ASJ AF: 0.372

Gnomad EAS AF: 0.263

Gnomad SAS AF: 0.298

Gnomad FIN AF: 0.284

Gnomad MID AF: 0.377

Gnomad NFE AF: 0.311

Gnomad OTH AF: 0.300

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

GnomAD4 genome AF: 0.315 AC: 47878 AN: 152010 Hom.: 7769 Cov.: 31 AF XY: 0.310 AC XY: 23058 AN XY: 74302

African (AFR) AF: 0.372 AC: 15418 AN: 41444

American (AMR) AF: 0.213 AC: 3250 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.372 AC: 1293 AN: 3472

East Asian (EAS) AF: 0.263 AC: 1354 AN: 5146

South Asian (SAS) AF: 0.298 AC: 1435 AN: 4812

European-Finnish (FIN) AF: 0.284 AC: 3013 AN: 10598

Middle Eastern (MID) AF: 0.388 AC: 114 AN: 294

European-Non Finnish (NFE) AF: 0.311 AC: 21137 AN: 67932

Other (OTH) AF: 0.297 AC: 627 AN: 2108

Alfa AF: 0.325 Hom.: 1575

Bravo AF: 0.313

Asia WGS AF: 0.303 AC: 1054 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	8.5
DANN	Benign	0.76
PhyloP100		0.76
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
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: rs2855804; hg19: chr6-31467365;