6-31508357-A-G

Position:

• chr6-31508357-A-G

Variant summary

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

The NM_005931.5(MICB):​c.1024+826A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.773 in 152,172 control chromosomes in the GnomAD database, including 45,736 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 0.77 (45736 hom., cov: 33)
• Consequence: MICB NM_005931.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.06

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=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.86 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MICB	NM_005931.5	c.1024+826A>G		intron_variant		ENST00000252229.7	NP_005922.2
MICB	NM_001289160.2	c.928+826A>G		intron_variant			NP_001276089.1
MICB	NM_001289161.2	c.895+826A>G		intron_variant			NP_001276090.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MICB	ENST00000252229.7	c.1024+826A>G		intron_variant		1	NM_005931.5	ENSP00000252229.6
MICB	ENST00000399150.7	c.895+826A>G		intron_variant		1		ENSP00000382103.3
MICB	ENST00000538442.5	c.928+826A>G		intron_variant		2		ENSP00000442345.1

Frequencies

GnomAD3 genomes AF: 0.773 AC: 117577 AN: 152054 Hom.: 45694 Cov.: 33

Gnomad AFR AF: 0.812

Gnomad AMI AF: 0.617

Gnomad AMR AF: 0.814

Gnomad ASJ AF: 0.899

Gnomad EAS AF: 0.881

Gnomad SAS AF: 0.834

Gnomad FIN AF: 0.658

Gnomad MID AF: 0.854

Gnomad NFE AF: 0.741

Gnomad OTH AF: 0.789

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

GnomAD4 genome AF: 0.773 AC: 117671 AN: 152172 Hom.: 45736 Cov.: 33 AF XY: 0.772 AC XY: 57405 AN XY: 74386

Gnomad4 AFR AF: 0.812

Gnomad4 AMR AF: 0.815

Gnomad4 ASJ AF: 0.899

Gnomad4 EAS AF: 0.881

Gnomad4 SAS AF: 0.835

Gnomad4 FIN AF: 0.658

Gnomad4 NFE AF: 0.741

Gnomad4 OTH AF: 0.791

Alfa AF: 0.758 Hom.: 21444

Bravo AF: 0.787

Asia WGS AF: 0.803 AC: 2790 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.87
DANN	Benign	0.60

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: rs3131635; hg19: chr6-31476134;