rs3134899

Positions:

• chr6-31505509-C-T

Variant summary

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

The NM_005931.5(MICB):​c.71-108C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.787 in 1,488,652 control chromosomes in the GnomAD database, including 463,851 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 0.80 (49327 hom., cov: 31)
  • Exomes 𝑓: 0.79 (414524 hom.)
• Consequence: MICB NM_005931.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.225

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=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.888 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MICB	NM_005931.5	c.71-108C>T		intron_variant		ENST00000252229.7
MICB	NM_001289160.2	c.-26-108C>T		intron_variant
MICB	NM_001289161.2	c.71-108C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MICB	ENST00000252229.7	c.71-108C>T		intron_variant		1	NM_005931.5	P1
MICB	ENST00000399150.7	c.71-108C>T		intron_variant		1
MICB	ENST00000538442.5	c.-26-108C>T		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.803 AC: 122051 AN: 152036 Hom.: 49274 Cov.: 31

Gnomad AFR AF: 0.835

Gnomad AMI AF: 0.769

Gnomad AMR AF: 0.844

Gnomad ASJ AF: 0.946

Gnomad EAS AF: 0.909

Gnomad SAS AF: 0.893

Gnomad FIN AF: 0.664

Gnomad MID AF: 0.867

Gnomad NFE AF: 0.773

Gnomad OTH AF: 0.822

GnomAD4 exome AF: 0.786 AC: 1050124 AN: 1336498 Hom.: 414524 AF XY: 0.790 AC XY: 520463 AN XY: 658870

Gnomad4 AFR exome AF: 0.840

Gnomad4 AMR exome AF: 0.860

Gnomad4 ASJ exome AF: 0.944

Gnomad4 EAS exome AF: 0.903

Gnomad4 SAS exome AF: 0.895

Gnomad4 FIN exome AF: 0.673

Gnomad4 NFE exome AF: 0.770

Gnomad4 OTH exome AF: 0.799

GnomAD4 genome AF: 0.803 AC: 122158 AN: 152154 Hom.: 49327 Cov.: 31 AF XY: 0.802 AC XY: 59635 AN XY: 74368

Gnomad4 AFR AF: 0.835

Gnomad4 AMR AF: 0.844

Gnomad4 ASJ AF: 0.946

Gnomad4 EAS AF: 0.909

Gnomad4 SAS AF: 0.892

Gnomad4 FIN AF: 0.664

Gnomad4 NFE AF: 0.773

Gnomad4 OTH AF: 0.823

Alfa AF: 0.796 Hom.: 85878

Bravo AF: 0.817

Asia WGS AF: 0.842 AC: 2927 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.70
DANN	Benign	0.67

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs3134899; hg19: chr6-31473286;