rs3130614

Variant names:

• chr6-31508681-T-A
• rs3130614
• NM_005931.5:c.1025-1101T>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.1025-1101T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0713 in 152,304 control chromosomes in the GnomAD database, including 562 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 0.071 (562 hom., cov: 33)
• Consequence: MICB NM_005931.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.339
• Publications: 34 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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.111 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005931.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MICB	NM_005931.5	MANE Select	c.1025-1101T>A		intron	N/A	NP_005922.2
	MICB	NM_001289160.2		c.929-1101T>A		intron	N/A	NP_001276089.1
	MICB	NM_001289161.2		c.896-1101T>A		intron	N/A	NP_001276090.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MICB	ENST00000252229.7	TSL:1 MANE Select	c.1025-1101T>A		intron	N/A	ENSP00000252229.6
	MICB	ENST00000399150.7	TSL:1	c.896-1101T>A		intron	N/A	ENSP00000382103.3
	MICB	ENST00000538442.5	TSL:2	c.929-1101T>A		intron	N/A	ENSP00000442345.1

Frequencies

GnomAD3 genomes AF: 0.0714 AC: 10862 AN: 152186 Hom.: 562 Cov.: 33

Gnomad AFR AF: 0.0349

Gnomad AMI AF: 0.148

Gnomad AMR AF: 0.0332

Gnomad ASJ AF: 0.0412

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0781

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.113

Gnomad OTH AF: 0.0507

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

GnomAD4 genome AF: 0.0713 AC: 10859 AN: 152304 Hom.: 562 Cov.: 33 AF XY: 0.0662 AC XY: 4933 AN XY: 74480

African (AFR) AF: 0.0348 AC: 1447 AN: 41568

American (AMR) AF: 0.0331 AC: 507 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.0412 AC: 143 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.0781 AC: 830 AN: 10622

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.113 AC: 7685 AN: 68004

Other (OTH) AF: 0.0502 AC: 106 AN: 2112

Alfa AF: 0.0994 Hom.: 120

Bravo AF: 0.0667

Asia WGS AF: 0.00635 AC: 23 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	6.2
DANN	Benign	0.64
PhyloP100		0.34
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs3130614; hg19: chr6-31476458;