6-31498140-G-T

Position:

• chr6-31498140-G-T

Variant summary

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

The ENST00000399150(MICB):​c.-54G>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0378 in 1,472,538 control chromosomes in the GnomAD database, including 1,346 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 0.033 (90 hom., cov: 31)
  • Exomes 𝑓: 0.038 (1256 hom.)
• Consequence: MICB ENST00000399150 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.454

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=-0.77).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0528 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MICB	NM_001289160.2	c.-27+3145G>T		intron_variant			NP_001276089.1
MICB	NM_005931.5	c.-54G>T		upstream_gene_variant		ENST00000252229.7	NP_005922.2
MICB	NM_001289161.2	c.-54G>T		upstream_gene_variant			NP_001276090.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MICB	ENST00000399150	c.-54G>T		5_prime_UTR_variant	1/6	1		ENSP00000382103.3
MICB	ENST00000538442.5	c.-27+3145G>T		intron_variant		2		ENSP00000442345.1
MICB	ENST00000252229.7	c.-54G>T		upstream_gene_variant		1	NM_005931.5	ENSP00000252229.6

Frequencies

GnomAD3 genomes AF: 0.0335 AC: 5090 AN: 152164 Hom.: 89 Cov.: 31

Gnomad AFR AF: 0.0249

Gnomad AMI AF: 0.152

Gnomad AMR AF: 0.0315

Gnomad ASJ AF: 0.0473

Gnomad EAS AF: 0.0278

Gnomad SAS AF: 0.0592

Gnomad FIN AF: 0.0124

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0386

Gnomad OTH AF: 0.0354

GnomAD4 exome AF: 0.0383 AC: 50595 AN: 1320256 Hom.: 1256 Cov.: 18 AF XY: 0.0387 AC XY: 25420 AN XY: 657500

Gnomad4 AFR exome AF: 0.0230

Gnomad4 AMR exome AF: 0.0316

Gnomad4 ASJ exome AF: 0.0488

Gnomad4 EAS exome AF: 0.0226

Gnomad4 SAS exome AF: 0.0550

Gnomad4 FIN exome AF: 0.0138

Gnomad4 NFE exome AF: 0.0391

Gnomad4 OTH exome AF: 0.0403

GnomAD4 genome AF: 0.0335 AC: 5101 AN: 152282 Hom.: 90 Cov.: 31 AF XY: 0.0335 AC XY: 2492 AN XY: 74460

Gnomad4 AFR AF: 0.0252

Gnomad4 AMR AF: 0.0316

Gnomad4 ASJ AF: 0.0473

Gnomad4 EAS AF: 0.0278

Gnomad4 SAS AF: 0.0584

Gnomad4 FIN AF: 0.0124

Gnomad4 NFE AF: 0.0386

Gnomad4 OTH AF: 0.0351

Alfa AF: 0.0239 Hom.: 22

Bravo AF: 0.0337

Asia WGS AF: 0.0400 AC: 138 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	3.8
DANN	Benign	0.60

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

Publications

LitVar

Other links and lift over

dbSNP: rs3828917; hg19: chr6-31465917;