rs2855804

chr6-31499588-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+1325C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.315 in 152,010 control chromosomes in the GnomAD database, including 7,769 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 0.31 (7769 hom., cov: 31)
• Consequence: MICB NM_005931.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.758

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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.367 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MICB	NM_005931.5	c.70+1325C>T		intron_variant		ENST00000252229.7
MICB	NM_001289160.2	c.-27+4593C>T		intron_variant
MICB	NM_001289161.2	c.70+1325C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MICB	ENST00000252229.7	c.70+1325C>T		intron_variant		1	NM_005931.5	P1
MICB	ENST00000399150.7	c.70+1325C>T		intron_variant		1
MICB	ENST00000538442.5	c.-27+4593C>T		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.315 AC: 47836 AN: 151892 Hom.: 7760 Cov.: 31

Gnomad AFR AF: 0.372

Gnomad AMI AF: 0.260

Gnomad AMR AF: 0.212

Gnomad ASJ AF: 0.372

Gnomad EAS AF: 0.263

Gnomad SAS AF: 0.298

Gnomad FIN AF: 0.284

Gnomad MID AF: 0.377

Gnomad NFE AF: 0.311

Gnomad OTH AF: 0.300

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

GnomAD4 genome AF: 0.315 AC: 47878 AN: 152010 Hom.: 7769 Cov.: 31 AF XY: 0.310 AC XY: 23058 AN XY: 74302

Gnomad4 AFR AF: 0.372

Gnomad4 AMR AF: 0.213

Gnomad4 ASJ AF: 0.372

Gnomad4 EAS AF: 0.263

Gnomad4 SAS AF: 0.298

Gnomad4 FIN AF: 0.284

Gnomad4 NFE AF: 0.311

Gnomad4 OTH AF: 0.297

Alfa AF: 0.325 Hom.: 1527

Bravo AF: 0.313

Asia WGS AF: 0.303 AC: 1054 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	8.5
Dann	Benign	0.76
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs2855804; hg19: chr6-31467365;