chr6-31498042-C-T

Position:

• chr6-31498042-C-T

Variant summary

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

The NM_001289160.2(MICB):​c.-27+3047C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.34 in 439,470 control chromosomes in the GnomAD database, including 25,412 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 0.38 (8453 hom., cov: 32)
  • Exomes 𝑓: 0.32 (16959 hom.)
• Consequence: MICB NM_001289160.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.269

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=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.488 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MICB	NM_001289160.2	c.-27+3047C>T		intron_variant			NP_001276089.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MICB	ENST00000538442.5	c.-27+3047C>T		intron_variant		2		ENSP00000442345
MICB	ENST00000399150.7			upstream_gene_variant		1		ENSP00000382103

Frequencies

GnomAD3 genomes AF: 0.383 AC: 50211 AN: 131142 Hom.: 8442 Cov.: 32

Gnomad AFR AF: 0.412

Gnomad AMI AF: 0.333

Gnomad AMR AF: 0.406

Gnomad ASJ AF: 0.409

Gnomad EAS AF: 0.505

Gnomad SAS AF: 0.440

Gnomad FIN AF: 0.342

Gnomad MID AF: 0.368

Gnomad NFE AF: 0.353

Gnomad OTH AF: 0.392

GnomAD4 exome AF: 0.322 AC: 99142 AN: 308224 Hom.: 16959 Cov.: 6 AF XY: 0.325 AC XY: 53556 AN XY: 164636

Gnomad4 AFR exome AF: 0.309

Gnomad4 AMR exome AF: 0.360

Gnomad4 ASJ exome AF: 0.332

Gnomad4 EAS exome AF: 0.498

Gnomad4 SAS exome AF: 0.368

Gnomad4 FIN exome AF: 0.304

Gnomad4 NFE exome AF: 0.303

Gnomad4 OTH exome AF: 0.328

GnomAD4 genome AF: 0.383 AC: 50252 AN: 131246 Hom.: 8453 Cov.: 32 AF XY: 0.384 AC XY: 24754 AN XY: 64424

Gnomad4 AFR AF: 0.412

Gnomad4 AMR AF: 0.406

Gnomad4 ASJ AF: 0.409

Gnomad4 EAS AF: 0.505

Gnomad4 SAS AF: 0.439

Gnomad4 FIN AF: 0.342

Gnomad4 NFE AF: 0.353

Gnomad4 OTH AF: 0.392

Alfa AF: 0.318 Hom.: 8468

Bravo AF: 0.333

Asia WGS AF: 0.378 AC: 1298 AN: 3436

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	7.7
DANN	Benign	0.56

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3828914; hg19: chr6-31465819; COSMIC: COSV52856596; COSMIC: COSV52856596;