rs2242955

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• 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: Benign. The variant received -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 rank	MANE	Protein	UniProt
MICB	NM_005931.5	c.613+73G>A		intron_variant	Intron 3 of 5	ENST00000252229.7	NP_005922.2
MICB	NM_001289160.2	c.517+73G>A		intron_variant	Intron 3 of 5		NP_001276089.1
MICB	NM_001289161.2	c.484+73G>A		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>A		intron_variant	Intron 3 of 5	1	NM_005931.5	ENSP00000252229.6
MICB	ENST00000399150.7	c.484+73G>A		intron_variant	Intron 3 of 5	1		ENSP00000382103.3
MICB	ENST00000538442.5	c.517+73G>A		intron_variant	Intron 3 of 5	2		ENSP00000442345.1
MICB	ENST00000494577.1	n.496+73G>A		intron_variant	Intron 1 of 2	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

African (AFR) AF: 0.131 AC: 4018 AN: 30564

American (AMR) AF: 0.0778 AC: 2761 AN: 35500

Ashkenazi Jewish (ASJ) AF: 0.0537 AC: 1170 AN: 21800

East Asian (EAS) AF: 0.134 AC: 5116 AN: 38234

South Asian (SAS) AF: 0.145 AC: 10745 AN: 74150

European-Finnish (FIN) AF: 0.151 AC: 7234 AN: 48028

Middle Eastern (MID) AF: 0.0950 AC: 514 AN: 5408

European-Non Finnish (NFE) AF: 0.117 AC: 122167 AN: 1047838

Other (OTH) AF: 0.113 AC: 6361 AN: 56342

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

African (AFR) AF: 0.132 AC: 5479 AN: 41534

American (AMR) AF: 0.0863 AC: 1320 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0493 AC: 171 AN: 3468

East Asian (EAS) AF: 0.132 AC: 681 AN: 5174

South Asian (SAS) AF: 0.153 AC: 736 AN: 4822

European-Finnish (FIN) AF: 0.149 AC: 1582 AN: 10610

Middle Eastern (MID) AF: 0.126 AC: 37 AN: 294

European-Non Finnish (NFE) AF: 0.117 AC: 7979 AN: 67992

Other (OTH) AF: 0.118 AC: 250 AN: 2114

Alfa AF: 0.109 Hom.: 1078

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
PhyloP100		-2.3
Mutation Taster		=100/0	polymorphism (auto)

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; COSMIC: COSV52856221;