chr6-31511209-C-T

Variant names:

• chr6-31511209-C-T
• rs2246618
• NM_005931.5:c.*1300C>T

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MICB	NM_005931.5	c.*1300C>T		downstream_gene_variant		ENST00000252229.7	NP_005922.2
MICB	NM_001289160.2	c.*1300C>T		downstream_gene_variant			NP_001276089.1
MICB	NM_001289161.2	c.*1300C>T		downstream_gene_variant			NP_001276090.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MICB	ENST00000252229.7	c.*1300C>T		downstream_gene_variant		1	NM_005931.5	ENSP00000252229.6
MICB	ENST00000399150.7	c.*1300C>T		downstream_gene_variant		1		ENSP00000382103.3
MICB	ENST00000538442.5	c.*1300C>T		downstream_gene_variant		2		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

Gnomad4 AFR exome AF: 0.500

Gnomad4 NFE exome AF: 0.500

Gnomad4 OTH exome AF: 0.00

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

Gnomad4 AFR AF: 0.372

Gnomad4 AMR AF: 0.208

Gnomad4 ASJ AF: 0.367

Gnomad4 EAS AF: 0.266

Gnomad4 SAS AF: 0.299

Gnomad4 FIN AF: 0.283

Gnomad4 NFE AF: 0.311

Gnomad4 OTH AF: 0.298

Alfa AF: 0.309 Hom.: 11379

Bravo AF: 0.313

Asia WGS AF: 0.303 AC: 1055 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.6
DANN	Benign	0.47

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2246618; hg19: chr6-31478986;