NM_005931.5:c.*1300C>T

Variant names:

• chr6-31511209-C-T
• rs2246618
• NM_005931.5:c.*1300C>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.*1300C>T variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.314 in 152,110 control chromosomes in the GnomAD database, including 7,752 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 (7752 hom., cov: 33)
  • Exomes 𝑓: 0.38 (0 hom.)
• Consequence: MICB NM_005931.5 downstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.788
• Publications: 44 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.367 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005931.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MICB	NM_005931.5	MANE Select	c.*1300C>T		downstream_gene	N/A	NP_005922.2
	MICB	NM_001289160.2		c.*1300C>T		downstream_gene	N/A	NP_001276089.1
	MICB	NM_001289161.2		c.*1300C>T		downstream_gene	N/A	NP_001276090.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MICB	ENST00000252229.7	TSL:1 MANE Select	c.*1300C>T		downstream_gene	N/A	ENSP00000252229.6
	MICB	ENST00000399150.7	TSL:1	c.*1300C>T		downstream_gene	N/A	ENSP00000382103.3
	MICB	ENST00000538442.5	TSL:2	c.*1300C>T		downstream_gene	N/A	ENSP00000442345.1

Frequencies

GnomAD3 genomes AF: 0.314 AC: 47755 AN: 151984 Hom.: 7743 Cov.: 33

Gnomad AFR AF: 0.372

Gnomad AMI AF: 0.260

Gnomad AMR AF: 0.208

Gnomad ASJ AF: 0.367

Gnomad EAS AF: 0.266

Gnomad SAS AF: 0.298

Gnomad FIN AF: 0.283

Gnomad MID AF: 0.373

Gnomad NFE AF: 0.311

Gnomad OTH AF: 0.300

GnomAD4 exome AF: 0.375 AC: 3 AN: 8 Hom.: 0 AF XY: 0.333 AC XY: 2 AN XY: 6

African (AFR) AF: 0.500 AC: 1 AN: 2

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.500 AC: 2 AN: 4

Other (OTH) AF: 0.00 AC: 0 AN: 2

GnomAD4 genome AF: 0.314 AC: 47797 AN: 152102 Hom.: 7752 Cov.: 33 AF XY: 0.309 AC XY: 22996 AN XY: 74342

African (AFR) AF: 0.372 AC: 15418 AN: 41478

American (AMR) AF: 0.208 AC: 3188 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.367 AC: 1272 AN: 3466

East Asian (EAS) AF: 0.266 AC: 1379 AN: 5180

South Asian (SAS) AF: 0.299 AC: 1439 AN: 4820

European-Finnish (FIN) AF: 0.283 AC: 2994 AN: 10570

Middle Eastern (MID) AF: 0.384 AC: 113 AN: 294

European-Non Finnish (NFE) AF: 0.311 AC: 21127 AN: 67974

Other (OTH) AF: 0.298 AC: 630 AN: 2116

Alfa AF: 0.316 Hom.: 28123

Bravo AF: 0.313

Asia WGS AF: 0.303 AC: 1055 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.6
DANN	Benign	0.47
PhyloP100		0.79
Mutation Taster		=100/0	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2246618; hg19: chr6-31478986;