rs3828875

Variant names:

• chr6-31411391-C-A
• rs3828875
• NM_001177519.3:c.613+32C>A

Your query was ambiguous. Multiple possible variants found:

• chr6-31411391-C-A
• chr6-31411391-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001177519.3(MICA):​c.613+32C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000727 in 1,375,822 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 7.3e-7 (0 hom.)
• Consequence: MICA NM_001177519.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.57
• Publications: 10 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MICA	NM_001177519.3	c.613+32C>A		intron_variant	Intron 3 of 5	ENST00000449934.7	NP_001170990.1
MICA	NM_001289152.2	c.322+32C>A		intron_variant	Intron 3 of 5		NP_001276081.1
MICA	NM_001289153.2	c.322+32C>A		intron_variant	Intron 3 of 5		NP_001276082.1
MICA	NM_001289154.2	c.199+32C>A		intron_variant	Intron 3 of 5		NP_001276083.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MICA	ENST00000449934.7	c.613+32C>A		intron_variant	Intron 3 of 5	1	NM_001177519.3	ENSP00000413079.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.27e-7 AC: 1 AN: 1375822 Hom.: 0 Cov.: 32 AF XY: 0.00000148 AC XY: 1 AN XY: 676564

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 30956

American (AMR) AF: 0.00 AC: 0 AN: 33344

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23182

East Asian (EAS) AF: 0.00 AC: 0 AN: 35568

South Asian (SAS) AF: 0.00 AC: 0 AN: 75590

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47584

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5584

European-Non Finnish (NFE) AF: 9.37e-7 AC: 1 AN: 1066992

Other (OTH) AF: 0.00 AC: 0 AN: 57022

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 612

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.3
DANN	Benign	0.77
PhyloP100		-1.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs3828875; hg19: chr6-31379168;