rs7756993

Variant names:

• chr6-31414356-T-C
• rs7756993
• NM_001177519.3:c.*30-656T>C

Your query was ambiguous. Multiple possible variants found:

• chr6-31414356-T-C
• chr6-31414356-T-G

Variant summary

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

The NM_001177519.3(MICA):​c.*30-656T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.32 in 151,424 control chromosomes in the GnomAD database, including 8,309 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 0.32 (8309 hom., cov: 33)
• Consequence: MICA NM_001177519.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.561
• Publications: 4 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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.393 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MICA	NM_001177519.3	c.*30-656T>C		intron_variant	Intron 5 of 5	ENST00000449934.7	NP_001170990.1
MICA	NM_001289152.2	c.*30-656T>C		intron_variant	Intron 5 of 5		NP_001276081.1
MICA	NM_001289153.2	c.*30-656T>C		intron_variant	Intron 5 of 5		NP_001276082.1
MICA	NM_001289154.2	c.*30-656T>C		intron_variant	Intron 5 of 5		NP_001276083.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MICA	ENST00000449934.7	c.*30-656T>C		intron_variant	Intron 5 of 5	1	NM_001177519.3	ENSP00000413079.1

Frequencies

GnomAD3 genomes AF: 0.320 AC: 48441 AN: 151306 Hom.: 8291 Cov.: 33

Gnomad AFR AF: 0.398

Gnomad AMI AF: 0.438

Gnomad AMR AF: 0.349

Gnomad ASJ AF: 0.351

Gnomad EAS AF: 0.317

Gnomad SAS AF: 0.305

Gnomad FIN AF: 0.369

Gnomad MID AF: 0.334

Gnomad NFE AF: 0.257

Gnomad OTH AF: 0.307

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

GnomAD4 genome AF: 0.320 AC: 48509 AN: 151424 Hom.: 8309 Cov.: 33 AF XY: 0.327 AC XY: 24176 AN XY: 73966

African (AFR) AF: 0.398 AC: 16414 AN: 41190

American (AMR) AF: 0.349 AC: 5303 AN: 15192

Ashkenazi Jewish (ASJ) AF: 0.351 AC: 1216 AN: 3468

East Asian (EAS) AF: 0.317 AC: 1627 AN: 5132

South Asian (SAS) AF: 0.304 AC: 1457 AN: 4790

European-Finnish (FIN) AF: 0.369 AC: 3871 AN: 10498

Middle Eastern (MID) AF: 0.346 AC: 101 AN: 292

European-Non Finnish (NFE) AF: 0.257 AC: 17469 AN: 67858

Other (OTH) AF: 0.311 AC: 652 AN: 2094

Alfa AF: 0.283 Hom.: 794

Bravo AF: 0.321

Asia WGS AF: 0.361 AC: 1254 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	3.0
DANN	Benign	0.59
PhyloP100		-0.56
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: rs7756993; hg19: chr6-31382133;