rs2855807

Positions:

• chr6-31501546-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.70+3283C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.654 in 152,026 control chromosomes in the GnomAD database, including 32,625 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 0.65 (32625 hom., cov: 32)
• Consequence: MICB NM_005931.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.11

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=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.709 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MICB	NM_005931.5	c.70+3283C>T		intron_variant		ENST00000252229.7
MICB	NM_001289160.2	c.-26-4071C>T		intron_variant
MICB	NM_001289161.2	c.70+3283C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MICB	ENST00000252229.7	c.70+3283C>T		intron_variant		1	NM_005931.5	P1
MICB	ENST00000399150.7	c.70+3283C>T		intron_variant		1
MICB	ENST00000538442.5	c.-26-4071C>T		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.654 AC: 99281 AN: 151906 Hom.: 32591 Cov.: 32

Gnomad AFR AF: 0.704

Gnomad AMI AF: 0.566

Gnomad AMR AF: 0.605

Gnomad ASJ AF: 0.804

Gnomad EAS AF: 0.729

Gnomad SAS AF: 0.696

Gnomad FIN AF: 0.593

Gnomad MID AF: 0.731

Gnomad NFE AF: 0.627

Gnomad OTH AF: 0.663

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

GnomAD4 genome AF: 0.654 AC: 99365 AN: 152026 Hom.: 32625 Cov.: 32 AF XY: 0.652 AC XY: 48411 AN XY: 74302

Gnomad4 AFR AF: 0.704

Gnomad4 AMR AF: 0.605

Gnomad4 ASJ AF: 0.804

Gnomad4 EAS AF: 0.728

Gnomad4 SAS AF: 0.696

Gnomad4 FIN AF: 0.593

Gnomad4 NFE AF: 0.628

Gnomad4 OTH AF: 0.661

Alfa AF: 0.637 Hom.: 9043

Bravo AF: 0.655

Asia WGS AF: 0.680 AC: 2363 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.5
DANN	Benign	0.18

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: rs2855807; hg19: chr6-31469323;