rs2242955

Positions:

• chr6-31506503-G-A
• chr6-31506503-G-C

Variant summary

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

The NM_005931.5(MICB):​c.613+73G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.118 in 1,510,080 control chromosomes in the GnomAD database, including 10,845 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 0.12 (1153 hom., cov: 32)
  • Exomes 𝑓: 0.12 (9692 hom.)
• Consequence: MICB NM_005931.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.26

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=-1.0).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.143 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MICB	NM_005931.5	c.613+73G>A		intron_variant		ENST00000252229.7
MICB	NM_001289160.2	c.517+73G>A		intron_variant
MICB	NM_001289161.2	c.484+73G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MICB	ENST00000252229.7	c.613+73G>A		intron_variant		1	NM_005931.5	P1
MICB	ENST00000399150.7	c.484+73G>A		intron_variant		1
MICB	ENST00000538442.5	c.517+73G>A		intron_variant		2
MICB	ENST00000494577.1	n.496+73G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.120 AC: 18237 AN: 152098 Hom.: 1152 Cov.: 32

Gnomad AFR AF: 0.132

Gnomad AMI AF: 0.0208

Gnomad AMR AF: 0.0858

Gnomad ASJ AF: 0.0493

Gnomad EAS AF: 0.131

Gnomad SAS AF: 0.153

Gnomad FIN AF: 0.149

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.117

Gnomad OTH AF: 0.119

GnomAD4 exome AF: 0.118 AC: 160086 AN: 1357864 Hom.: 9692 AF XY: 0.119 AC XY: 79723 AN XY: 671802

Gnomad4 AFR exome AF: 0.131

Gnomad4 AMR exome AF: 0.0778

Gnomad4 ASJ exome AF: 0.0537

Gnomad4 EAS exome AF: 0.134

Gnomad4 SAS exome AF: 0.145

Gnomad4 FIN exome AF: 0.151

Gnomad4 NFE exome AF: 0.117

Gnomad4 OTH exome AF: 0.113

GnomAD4 genome AF: 0.120 AC: 18254 AN: 152216 Hom.: 1153 Cov.: 32 AF XY: 0.120 AC XY: 8966 AN XY: 74426

Gnomad4 AFR AF: 0.132

Gnomad4 AMR AF: 0.0863

Gnomad4 ASJ AF: 0.0493

Gnomad4 EAS AF: 0.132

Gnomad4 SAS AF: 0.153

Gnomad4 FIN AF: 0.149

Gnomad4 NFE AF: 0.117

Gnomad4 OTH AF: 0.118

Alfa AF: 0.107 Hom.: 776

Bravo AF: 0.116

Asia WGS AF: 0.145 AC: 507 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.46
DANN	Benign	0.67

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: rs2242955; hg19: chr6-31474280; COSMIC: COSV52856221;