6-31506223-G-A

Variant names:

• chr6-31506223-G-A
• rs1051788
• NM_005931.5:c.406G>A

Variant summary

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

The NM_005931.5(MICB):​c.406G>A​(p.Asp136Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.305 in 1,613,810 control chromosomes in the GnomAD database, including 76,980 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.31 (7768 hom., cov: 32)
  • Exomes 𝑓: 0.30 (69212 hom.)
• Consequence: MICB NM_005931.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.615
• Publications: 42 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 (MetaRNN=0.0043391287).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.367 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MICB	NM_005931.5	c.406G>A	p.Asp136Asn	missense_variant	Exon 3 of 6	ENST00000252229.7	NP_005922.2
MICB	NM_001289160.2	c.310G>A	p.Asp104Asn	missense_variant	Exon 3 of 6		NP_001276089.1
MICB	NM_001289161.2	c.326-49G>A		intron_variant	Intron 2 of 5		NP_001276090.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MICB	ENST00000252229.7	c.406G>A	p.Asp136Asn	missense_variant	Exon 3 of 6	1	NM_005931.5	ENSP00000252229.6
MICB	ENST00000399150.7	c.326-49G>A		intron_variant	Intron 2 of 5	1		ENSP00000382103.3
MICB	ENST00000538442.5	c.310G>A	p.Asp104Asn	missense_variant	Exon 3 of 6	2		ENSP00000442345.1
MICB	ENST00000494577.1	n.289G>A		non_coding_transcript_exon_variant	Exon 1 of 3	3

Frequencies

GnomAD3 genomes AF: 0.314 AC: 47742 AN: 151852 Hom.: 7759 Cov.: 32

Gnomad AFR AF: 0.372

Gnomad AMI AF: 0.260

Gnomad AMR AF: 0.209

Gnomad ASJ AF: 0.367

Gnomad EAS AF: 0.263

Gnomad SAS AF: 0.297

Gnomad FIN AF: 0.284

Gnomad MID AF: 0.373

Gnomad NFE AF: 0.311

Gnomad OTH AF: 0.301

GnomAD2 exomes AF: 0.293 AC: 72991 AN: 249430 AF XY: 0.299

Gnomad AFR exome AF: 0.376

Gnomad AMR exome AF: 0.156

Gnomad ASJ exome AF: 0.356

Gnomad EAS exome AF: 0.275

Gnomad FIN exome AF: 0.287

Gnomad NFE exome AF: 0.319

Gnomad OTH exome AF: 0.278

GnomAD4 exome AF: 0.304 AC: 444598 AN: 1461840 Hom.: 69212 Cov.: 56 AF XY: 0.306 AC XY: 222666 AN XY: 727206

African (AFR) AF: 0.378 AC: 12654 AN: 33480

American (AMR) AF: 0.167 AC: 7447 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.356 AC: 9293 AN: 26136

East Asian (EAS) AF: 0.213 AC: 8444 AN: 39700

South Asian (SAS) AF: 0.313 AC: 26959 AN: 86256

European-Finnish (FIN) AF: 0.284 AC: 15186 AN: 53400

Middle Eastern (MID) AF: 0.305 AC: 1759 AN: 5766

European-Non Finnish (NFE) AF: 0.310 AC: 344263 AN: 1111986

Other (OTH) AF: 0.308 AC: 18593 AN: 60394

GnomAD4 genome AF: 0.314 AC: 47784 AN: 151970 Hom.: 7768 Cov.: 32 AF XY: 0.310 AC XY: 22997 AN XY: 74296

African (AFR) AF: 0.372 AC: 15418 AN: 41414

American (AMR) AF: 0.209 AC: 3192 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.367 AC: 1275 AN: 3472

East Asian (EAS) AF: 0.263 AC: 1359 AN: 5162

South Asian (SAS) AF: 0.298 AC: 1433 AN: 4816

European-Finnish (FIN) AF: 0.284 AC: 3004 AN: 10574

Middle Eastern (MID) AF: 0.384 AC: 113 AN: 294

European-Non Finnish (NFE) AF: 0.311 AC: 21124 AN: 67928

Other (OTH) AF: 0.298 AC: 629 AN: 2110

Alfa AF: 0.299 Hom.: 4439

Bravo AF: 0.313

TwinsUK AF: 0.321 AC: 1190

ALSPAC AF: 0.301 AC: 1161

ESP6500AA AF: 0.368 AC: 1409

ESP6500EA AF: 0.307 AC: 2523

ExAC AF: 0.302 AC: 36524

Asia WGS AF: 0.303 AC: 1055 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.77	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	6.3
DANN	Benign	0.86
DEOGEN2	Benign	0.071	T;.
Eigen	Benign	-0.96
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.029	N
MetaRNN	Benign	0.0043	T;T
MetaSVM	Benign	-0.94	T
PhyloP100		0.61
PrimateAI	Benign	0.26	T
PROVEAN	Uncertain	-3.2	D;D
REVEL	Benign	0.058
Sift	Benign	0.33	T;T
Sift4G	Benign	0.56	T;T
Polyphen		0.077	B;.
Vest4		0.079
MPC		0.26
ClinPred		0.017	T
GERP RS		-0.60
gMVP		0.47
Mutation Taster		=99/1	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs1051788; hg19: chr6-31474000; COSMIC: COSV52856573;