6-31401187-C-T

Variant names:

• chr6-31401187-C-T
• rs2844521
• NM_001289152.2:c.-222+404C>T

Variant summary

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

The NM_001289152.2(MICA):​c.-222+404C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.41 in 151,126 control chromosomes in the GnomAD database, including 13,637 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 0.41 (13637 hom., cov: 30)
• Consequence: MICA NM_001289152.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.249
• Publications: 23 publications found

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]

ENSG00000288587 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.517 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MICA	NM_001289152.2	c.-222+404C>T		intron_variant	Intron 1 of 5		NP_001276081.1
MICA	NM_001289153.2	c.-222+424C>T		intron_variant	Intron 1 of 5		NP_001276082.1
MICA	NM_001289154.2	c.-173+424C>T		intron_variant	Intron 1 of 5		NP_001276083.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MICA	ENST00000616296.4	c.-222+404C>T		intron_variant	Intron 1 of 5	5		ENSP00000482382.1
MICA	ENST00000674069.1	c.-173+424C>T		intron_variant	Intron 1 of 5			ENSP00000501157.1
MICA	ENST00000673647.1	c.-389+424C>T		intron_variant	Intron 1 of 3			ENSP00000500967.1

Frequencies

GnomAD3 genomes AF: 0.410 AC: 61874 AN: 151004 Hom.: 13616 Cov.: 30

Gnomad AFR AF: 0.523

Gnomad AMI AF: 0.493

Gnomad AMR AF: 0.496

Gnomad ASJ AF: 0.633

Gnomad EAS AF: 0.289

Gnomad SAS AF: 0.395

Gnomad FIN AF: 0.344

Gnomad MID AF: 0.490

Gnomad NFE AF: 0.329

Gnomad OTH AF: 0.462

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

GnomAD4 genome AF: 0.410 AC: 61948 AN: 151126 Hom.: 13637 Cov.: 30 AF XY: 0.411 AC XY: 30323 AN XY: 73792

African (AFR) AF: 0.523 AC: 21437 AN: 41010

American (AMR) AF: 0.496 AC: 7477 AN: 15078

Ashkenazi Jewish (ASJ) AF: 0.633 AC: 2185 AN: 3450

East Asian (EAS) AF: 0.289 AC: 1484 AN: 5130

South Asian (SAS) AF: 0.394 AC: 1891 AN: 4796

European-Finnish (FIN) AF: 0.344 AC: 3608 AN: 10494

Middle Eastern (MID) AF: 0.483 AC: 141 AN: 292

European-Non Finnish (NFE) AF: 0.329 AC: 22309 AN: 67882

Other (OTH) AF: 0.464 AC: 973 AN: 2096

Alfa AF: 0.359 Hom.: 25918

Bravo AF: 0.430

Asia WGS AF: 0.346 AC: 1202 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	4.7
DANN	Benign	0.58
PhyloP100		0.25
PromoterAI		0.0050	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2844521; hg19: chr6-31368964;