6-31412672-C-T

Position:

• chr6-31412672-C-T

Variant summary

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

The NM_001177519.3(MICA):​c.*29+212C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.548 in 151,566 control chromosomes in the GnomAD database, including 24,021 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 0.55 (24021 hom., cov: 31)
• Consequence: MICA NM_001177519.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.391

Genes affected

MICA (HGNC:7090): (MHC class I polypeptide-related sequence A) This gene encodes the highly polymorphic major histocompatability complex class I chain-related protein A. The protein product is expressed on the cell surface, although unlike canonical class I molecules it does not seem to associate with beta-2-microglobulin. It is a ligand for the NKG2-D type II integral membrane protein receptor. The protein functions as a stress-induced antigen that is broadly recognized by intestinal epithelial gamma delta T cells. Variations in this gene have been associated with susceptibility to psoriasis 1 and psoriatic arthritis, and the shedding of MICA-related antibodies and ligands is involved in the progression from monoclonal gammopathy of undetermined significance to multiple myeloma. Alternative splicing of this gene 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=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.667 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MICA	NM_001177519.3	c.*29+212C>T		intron_variant		ENST00000449934.7	NP_001170990.1
MICA	NM_001289152.2	c.*29+212C>T		intron_variant			NP_001276081.1
MICA	NM_001289153.2	c.*29+212C>T		intron_variant			NP_001276082.1
MICA	NM_001289154.2	c.*29+212C>T		intron_variant			NP_001276083.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MICA	ENST00000449934.7	c.*29+212C>T		intron_variant		1	NM_001177519.3	ENSP00000413079	P1
MICA	ENST00000421350.1	c.*29+212C>T		intron_variant		5		ENSP00000402410
MICA	ENST00000616296.4	c.*29+212C>T		intron_variant		5		ENSP00000482382
MICA	ENST00000674069.1	c.*29+212C>T		intron_variant				ENSP00000501157

Frequencies

GnomAD3 genomes AF: 0.547 AC: 82915 AN: 151450 Hom.: 23983 Cov.: 31

Gnomad AFR AF: 0.674

Gnomad AMI AF: 0.546

Gnomad AMR AF: 0.634

Gnomad ASJ AF: 0.805

Gnomad EAS AF: 0.437

Gnomad SAS AF: 0.600

Gnomad FIN AF: 0.452

Gnomad MID AF: 0.764

Gnomad NFE AF: 0.454

Gnomad OTH AF: 0.645

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

GnomAD4 genome AF: 0.548 AC: 83004 AN: 151566 Hom.: 24021 Cov.: 31 AF XY: 0.551 AC XY: 40834 AN XY: 74052

Gnomad4 AFR AF: 0.674

Gnomad4 AMR AF: 0.635

Gnomad4 ASJ AF: 0.805

Gnomad4 EAS AF: 0.438

Gnomad4 SAS AF: 0.600

Gnomad4 FIN AF: 0.452

Gnomad4 NFE AF: 0.454

Gnomad4 OTH AF: 0.644

Alfa AF: 0.491 Hom.: 18651

Bravo AF: 0.568

Asia WGS AF: 0.559 AC: 1942 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.5
DANN	Benign	0.67

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs2256175; hg19: chr6-31380449;