rs4713468

chr6-31503098-T-A

Variant summary

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

The NM_005931.5(MICB):c.71-2519T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.338 in 152,072 control chromosomes in the GnomAD database, including 8,836 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 0.34 (8836 hom., cov: 33)
• Consequence: MICB NM_005931.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0970

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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.447 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MICB	NM_005931.5	c.71-2519T>A		intron_variant		ENST00000252229.7
MICB	NM_001289160.2	c.-26-2519T>A		intron_variant
MICB	NM_001289161.2	c.71-2519T>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MICB	ENST00000252229.7	c.71-2519T>A		intron_variant		1	NM_005931.5	P1
MICB	ENST00000399150.7	c.71-2519T>A		intron_variant		1
MICB	ENST00000538442.5	c.-26-2519T>A		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.338 AC: 51385 AN: 151954 Hom.: 8824 Cov.: 33

Gnomad AFR AF: 0.330

Gnomad AMI AF: 0.307

Gnomad AMR AF: 0.395

Gnomad ASJ AF: 0.433

Gnomad EAS AF: 0.463

Gnomad SAS AF: 0.397

Gnomad FIN AF: 0.307

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.316

Gnomad OTH AF: 0.361

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

GnomAD4 genome AF: 0.338 AC: 51425 AN: 152072 Hom.: 8836 Cov.: 33 AF XY: 0.341 AC XY: 25324 AN XY: 74338

Gnomad4 AFR AF: 0.331

Gnomad4 AMR AF: 0.394

Gnomad4 ASJ AF: 0.433

Gnomad4 EAS AF: 0.462

Gnomad4 SAS AF: 0.397

Gnomad4 FIN AF: 0.307

Gnomad4 NFE AF: 0.316

Gnomad4 OTH AF: 0.362

Alfa AF: 0.326 Hom.: 1006

Bravo AF: 0.342

Asia WGS AF: 0.376 AC: 1307 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	4.1
Dann	Benign	0.36

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: rs4713468; hg19: chr6-31470875;