6-31506503-G-C

Variant names:

• chr6-31506503-G-C
• rs2242955
• NM_005931.5:c.613+73G>C

Variant summary

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

The NM_005931.5(MICB):​c.613+73G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000736 in 1,358,604 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: 7.4e-7 (0 hom.)
• Consequence: MICB NM_005931.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.26
• Publications: 18 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=-1.0).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MICB	NM_005931.5	c.613+73G>C		intron_variant	Intron 3 of 5	ENST00000252229.7	NP_005922.2
MICB	NM_001289160.2	c.517+73G>C		intron_variant	Intron 3 of 5		NP_001276089.1
MICB	NM_001289161.2	c.484+73G>C		intron_variant	Intron 3 of 5		NP_001276090.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MICB	ENST00000252229.7	c.613+73G>C		intron_variant	Intron 3 of 5	1	NM_005931.5	ENSP00000252229.6
MICB	ENST00000399150.7	c.484+73G>C		intron_variant	Intron 3 of 5	1		ENSP00000382103.3
MICB	ENST00000538442.5	c.517+73G>C		intron_variant	Intron 3 of 5	2		ENSP00000442345.1
MICB	ENST00000494577.1	n.496+73G>C		intron_variant	Intron 1 of 2	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.36e-7 AC: 1 AN: 1358604 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 672136

African (AFR) AF: 0.00 AC: 0 AN: 30578

American (AMR) AF: 0.00 AC: 0 AN: 35514

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21800

East Asian (EAS) AF: 0.00 AC: 0 AN: 38242

South Asian (SAS) AF: 0.00 AC: 0 AN: 74188

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48054

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5410

European-Non Finnish (NFE) AF: 9.54e-7 AC: 1 AN: 1048464

Other (OTH) AF: 0.00 AC: 0 AN: 56354

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 1078

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.16
DANN	Benign	0.50
PhyloP100		-2.3

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

Other links and lift over

dbSNP: rs2242955; hg19: chr6-31474280;