6-31498138-G-C

Variant names:

• chr6-31498138-G-C
• rs3828916
• ENST00000399150.7:c.-56G>C

Variant summary

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

The ENST00000399150.7(MICB):​c.-56G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.788 in 1,445,658 control chromosomes in the GnomAD database, including 451,173 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 0.80 (49318 hom., cov: 33)
  • Exomes 𝑓: 0.79 (401855 hom.)
• Consequence: MICB ENST00000399150.7 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.67
• Publications: 13 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.887 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MICB	NM_001289160.2	c.-27+3143G>C		intron_variant	Intron 1 of 5		NP_001276089.1
MICB	NM_005931.5	c.-56G>C		upstream_gene_variant		ENST00000252229.7	NP_005922.2
MICB	NM_001289161.2	c.-56G>C		upstream_gene_variant			NP_001276090.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MICB	ENST00000399150.7	c.-56G>C		5_prime_UTR_variant	Exon 1 of 6	1		ENSP00000382103.3
MICB	ENST00000538442.5	c.-27+3143G>C		intron_variant	Intron 1 of 5	2		ENSP00000442345.1
MICB	ENST00000252229.7	c.-56G>C		upstream_gene_variant		1	NM_005931.5	ENSP00000252229.6

Frequencies

GnomAD3 genomes AF: 0.803 AC: 122045 AN: 152042 Hom.: 49265 Cov.: 33

Gnomad AFR AF: 0.835

Gnomad AMI AF: 0.769

Gnomad AMR AF: 0.844

Gnomad ASJ AF: 0.945

Gnomad EAS AF: 0.909

Gnomad SAS AF: 0.892

Gnomad FIN AF: 0.665

Gnomad MID AF: 0.867

Gnomad NFE AF: 0.773

Gnomad OTH AF: 0.823

GnomAD4 exome AF: 0.786 AC: 1016830 AN: 1293498 Hom.: 401855 Cov.: 17 AF XY: 0.791 AC XY: 509216 AN XY: 643858

African (AFR) AF: 0.841 AC: 23394 AN: 27822

American (AMR) AF: 0.857 AC: 30886 AN: 36044

Ashkenazi Jewish (ASJ) AF: 0.945 AC: 20780 AN: 21986

East Asian (EAS) AF: 0.903 AC: 26344 AN: 29184

South Asian (SAS) AF: 0.895 AC: 70252 AN: 78488

European-Finnish (FIN) AF: 0.672 AC: 32690 AN: 48630

Middle Eastern (MID) AF: 0.877 AC: 4620 AN: 5268

European-Non Finnish (NFE) AF: 0.771 AC: 766169 AN: 993978

Other (OTH) AF: 0.800 AC: 41695 AN: 52098

GnomAD4 genome AF: 0.803 AC: 122152 AN: 152160 Hom.: 49318 Cov.: 33 AF XY: 0.802 AC XY: 59638 AN XY: 74396

African (AFR) AF: 0.835 AC: 34677 AN: 41510

American (AMR) AF: 0.844 AC: 12922 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.945 AC: 3282 AN: 3472

East Asian (EAS) AF: 0.909 AC: 4711 AN: 5182

South Asian (SAS) AF: 0.892 AC: 4306 AN: 4828

European-Finnish (FIN) AF: 0.665 AC: 7030 AN: 10564

Middle Eastern (MID) AF: 0.861 AC: 253 AN: 294

European-Non Finnish (NFE) AF: 0.773 AC: 52530 AN: 67984

Other (OTH) AF: 0.825 AC: 1740 AN: 2110

Alfa AF: 0.702 Hom.: 1987

Bravo AF: 0.817

Asia WGS AF: 0.842 AC: 2925 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	1.8
DANN	Benign	0.59
PhyloP100		-1.7
PromoterAI		-0.033	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs3828916; hg19: chr6-31465915;