NM_005931.5:c.71-352T>C

Variant names:

• chr6-31505265-T-C
• rs2855814
• NM_005931.5:c.71-352T>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.71-352T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.119 in 152,102 control chromosomes in the GnomAD database, including 1,204 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 (1204 hom., cov: 31)
• Consequence: MICB NM_005931.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.534
• Publications: 6 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=-0.99).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.202 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MICB	NM_005931.5	c.71-352T>C		intron_variant	Intron 1 of 5	ENST00000252229.7	NP_005922.2
MICB	NM_001289160.2	c.-26-352T>C		intron_variant	Intron 1 of 5		NP_001276089.1
MICB	NM_001289161.2	c.71-352T>C		intron_variant	Intron 1 of 5		NP_001276090.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MICB	ENST00000252229.7	c.71-352T>C		intron_variant	Intron 1 of 5	1	NM_005931.5	ENSP00000252229.6
MICB	ENST00000399150.7	c.71-352T>C		intron_variant	Intron 1 of 5	1		ENSP00000382103.3
MICB	ENST00000538442.5	c.-26-352T>C		intron_variant	Intron 1 of 5	2		ENSP00000442345.1

Frequencies

GnomAD3 genomes AF: 0.119 AC: 18136 AN: 151984 Hom.: 1203 Cov.: 31

Gnomad AFR AF: 0.119

Gnomad AMI AF: 0.0504

Gnomad AMR AF: 0.208

Gnomad ASJ AF: 0.0943

Gnomad EAS AF: 0.152

Gnomad SAS AF: 0.137

Gnomad FIN AF: 0.0598

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.107

Gnomad OTH AF: 0.125

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.119 AC: 18153 AN: 152102 Hom.: 1204 Cov.: 31 AF XY: 0.120 AC XY: 8924 AN XY: 74352

African (AFR) AF: 0.119 AC: 4938 AN: 41496

American (AMR) AF: 0.208 AC: 3176 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.0943 AC: 327 AN: 3466

East Asian (EAS) AF: 0.153 AC: 788 AN: 5164

South Asian (SAS) AF: 0.137 AC: 658 AN: 4816

European-Finnish (FIN) AF: 0.0598 AC: 634 AN: 10608

Middle Eastern (MID) AF: 0.112 AC: 33 AN: 294

European-Non Finnish (NFE) AF: 0.107 AC: 7281 AN: 67976

Other (OTH) AF: 0.129 AC: 272 AN: 2108

Alfa AF: 0.111 Hom.: 130

Bravo AF: 0.133

Asia WGS AF: 0.124 AC: 432 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	3.5
DANN	Benign	0.41
PhyloP100		-0.53
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
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: rs2855814; hg19: chr6-31473042; COSMIC: COSV52857947; COSMIC: COSV52857947;