rs6916394

Positions:

• chr6-31496273-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001289160.2(MICB):​c.-27+1278T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.338 in 152,098 control chromosomes in the GnomAD database, including 8,844 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 0.34 (8844 hom., cov: 33)
• Consequence: MICB NM_001289160.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0940

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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.448 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MICB	NM_001289160.2	c.-27+1278T>C		intron_variant			NP_001276089.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MICB	ENST00000538442.5	c.-27+1278T>C		intron_variant		2		ENSP00000442345

Frequencies

GnomAD3 genomes AF: 0.338 AC: 51386 AN: 151980 Hom.: 8832 Cov.: 33

Gnomad AFR AF: 0.330

Gnomad AMI AF: 0.306

Gnomad AMR AF: 0.394

Gnomad ASJ AF: 0.432

Gnomad EAS AF: 0.464

Gnomad SAS AF: 0.397

Gnomad FIN AF: 0.307

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.316

Gnomad OTH AF: 0.361

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

GnomAD4 genome AF: 0.338 AC: 51425 AN: 152098 Hom.: 8844 Cov.: 33 AF XY: 0.341 AC XY: 25307 AN XY: 74318

Gnomad4 AFR AF: 0.331

Gnomad4 AMR AF: 0.394

Gnomad4 ASJ AF: 0.432

Gnomad4 EAS AF: 0.463

Gnomad4 SAS AF: 0.397

Gnomad4 FIN AF: 0.307

Gnomad4 NFE AF: 0.316

Gnomad4 OTH AF: 0.362

Alfa AF: 0.330 Hom.: 5734

Bravo AF: 0.342

Asia WGS AF: 0.375 AC: 1302 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	5.8
DANN	Benign	0.78

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs6916394; hg19: chr6-31464050;