6-31498042-C-G

Variant names:

• chr6-31498042-C-G
• rs3828914
• NM_001289160.2:c.-27+3047C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001289160.2(MICB):​c.-27+3047C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000646 in 309,370 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000065 (0 hom.)
• Consequence: MICB NM_001289160.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.269
• Publications: 35 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]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MICB	NM_001289160.2	c.-27+3047C>G		intron_variant	Intron 1 of 5		NP_001276089.1
MICB	NM_005931.5	c.-152C>G		upstream_gene_variant		ENST00000252229.7	NP_005922.2
MICB	NM_001289161.2	c.-152C>G		upstream_gene_variant			NP_001276090.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MICB	ENST00000538442.5	c.-27+3047C>G		intron_variant	Intron 1 of 5	2		ENSP00000442345.1
MICB	ENST00000252229.7	c.-152C>G		upstream_gene_variant		1	NM_005931.5	ENSP00000252229.6
MICB	ENST00000399150.7	c.-152C>G		upstream_gene_variant		1		ENSP00000382103.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000646 AC: 2 AN: 309370 Hom.: 0 Cov.: 6 AF XY: 0.00000605 AC XY: 1 AN XY: 165218

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 5012

American (AMR) AF: 0.00 AC: 0 AN: 7756

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 6840

East Asian (EAS) AF: 0.00 AC: 0 AN: 9420

South Asian (SAS) AF: 0.00 AC: 0 AN: 40086

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 23382

Middle Eastern (MID) AF: 0.000414 AC: 1 AN: 2416

European-Non Finnish (NFE) AF: 0.00000501 AC: 1 AN: 199700

Other (OTH) AF: 0.00 AC: 0 AN: 14758

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	6.9
DANN	Benign	0.23
PhyloP100		0.27
PromoterAI		0.014	Neutral

Splicing

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

Other links and lift over

dbSNP: rs3828914; hg19: chr6-31465819;