rs2857281

Variant names:

• chr6-31406485-A-C
• rs2857281
• NM_001177519.3:c.70+2783A>C

Variant summary

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

The NM_001177519.3(MICA):​c.70+2783A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.107 in 151,148 control chromosomes in the GnomAD database, including 1,300 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 0.11 (1300 hom., cov: 32)
• Consequence: MICA NM_001177519.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.338
• Publications: 9 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.167 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001177519.3. 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
	MICA	NM_001177519.3	MANE Select	c.70+2783A>C		intron	N/A	NP_001170990.1
	MICA	NM_001289152.2		c.-221-4058A>C		intron	N/A	NP_001276081.1
	MICA	NM_001289153.2		c.-221-4058A>C		intron	N/A	NP_001276082.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MICA	ENST00000449934.7	TSL:1 MANE Select	c.70+2783A>C		intron	N/A	ENSP00000413079.1
	MICA	ENST00000616296.4	TSL:5	c.-221-4058A>C		intron	N/A	ENSP00000482382.1
	MICA	ENST00000421350.1	TSL:5	c.31+2783A>C		intron	N/A	ENSP00000402410.1

Frequencies

GnomAD3 genomes AF: 0.107 AC: 16115 AN: 151030 Hom.: 1295 Cov.: 32

Gnomad AFR AF: 0.170

Gnomad AMI AF: 0.0263

Gnomad AMR AF: 0.140

Gnomad ASJ AF: 0.0713

Gnomad EAS AF: 0.0784

Gnomad SAS AF: 0.112

Gnomad FIN AF: 0.00784

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.0796

Gnomad OTH AF: 0.150

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

GnomAD4 genome AF: 0.107 AC: 16134 AN: 151148 Hom.: 1300 Cov.: 32 AF XY: 0.104 AC XY: 7662 AN XY: 73846

African (AFR) AF: 0.170 AC: 6976 AN: 40982

American (AMR) AF: 0.139 AC: 2110 AN: 15128

Ashkenazi Jewish (ASJ) AF: 0.0713 AC: 246 AN: 3450

East Asian (EAS) AF: 0.0784 AC: 403 AN: 5138

South Asian (SAS) AF: 0.112 AC: 536 AN: 4790

European-Finnish (FIN) AF: 0.00784 AC: 82 AN: 10462

Middle Eastern (MID) AF: 0.126 AC: 37 AN: 294

European-Non Finnish (NFE) AF: 0.0797 AC: 5408 AN: 67890

Other (OTH) AF: 0.148 AC: 312 AN: 2102

Alfa AF: 0.0890 Hom.: 634

Bravo AF: 0.122

Asia WGS AF: 0.110 AC: 382 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	12
DANN	Benign	0.79
PhyloP100		0.34
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2857281; hg19: chr6-31374262;