chr6-31496962-G-A

Variant names:

• chr6-31496962-G-A
• rs3828903
• NM_001289160.2:c.-27+1967G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001289160.2(MICB):​c.-27+1967G>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 151,988 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: 31)
• Consequence: MICB NM_001289160.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.201
• Publications: 43 publications found

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]

Y_RNA (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.447 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001289160.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MICB	NM_001289160.2		c.-27+1967G>A		intron	N/A	NP_001276089.1	F5H7Q8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MICB	ENST00000538442.5	TSL:2	c.-27+1967G>A		intron	N/A	ENSP00000442345.1	F5H7Q8
	Y_RNA	ENST00000383850.1	TSL:6	n.-172C>T		upstream_gene	N/A

Frequencies

GnomAD3 genomes AF: 0.338 AC: 51366 AN: 151870 Hom.: 8824 Cov.: 31

Gnomad AFR AF: 0.331

Gnomad AMI AF: 0.304

Gnomad AMR AF: 0.395

Gnomad ASJ AF: 0.432

Gnomad EAS AF: 0.463

Gnomad SAS AF: 0.398

Gnomad FIN AF: 0.308

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.316

Gnomad OTH AF: 0.363

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

GnomAD4 genome AF: 0.338 AC: 51405 AN: 151988 Hom.: 8836 Cov.: 31 AF XY: 0.341 AC XY: 25328 AN XY: 74314

African (AFR) AF: 0.331 AC: 13710 AN: 41448

American (AMR) AF: 0.395 AC: 6030 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.432 AC: 1499 AN: 3466

East Asian (EAS) AF: 0.463 AC: 2382 AN: 5146

South Asian (SAS) AF: 0.397 AC: 1914 AN: 4818

European-Finnish (FIN) AF: 0.308 AC: 3253 AN: 10574

Middle Eastern (MID) AF: 0.340 AC: 100 AN: 294

European-Non Finnish (NFE) AF: 0.316 AC: 21476 AN: 67952

Other (OTH) AF: 0.363 AC: 764 AN: 2102

Alfa AF: 0.325 Hom.: 34734

Bravo AF: 0.342

Asia WGS AF: 0.376 AC: 1305 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	11
DANN	Benign	0.71
PhyloP100		-0.20
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs3828903; hg19: chr6-31464739;