22-26668613-G-A

Position:

• chr22-26668613-G-A

Variant summary

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

The ENST00000613780.4(MIAT):​n.2281G>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.117 in 398,884 control chromosomes in the GnomAD database, including 2,945 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as no classification for the single variant (no stars).

• Frequency:
  • Genomes: 𝑓 0.11 (974 hom., cov: 33)
  • Exomes 𝑓: 0.12 (1971 hom.)
• Consequence: MIAT ENST00000613780.4 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0210

Genes affected

MIAT (HGNC:33425): (myocardial infarction associated transcript) This gene encodes a spliced long non-coding RNA that may constitute a component of the nuclear matrix. Altered expression of this locus has been reported to be associated with a susceptibility to myocardial infarction. It has also been proposed that pathways involving this transcript may contribute to the pathophysiology of schizophrenia. A similar gene in mouse has been associated with retinal cell fate determination. Alternatively spliced transcript variants have been identified. [provided by RefSeq, Dec 2014]

ENSG00000206028 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.13 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MIAT	NR_003491.4	n.2213G>A		non_coding_transcript_exon_variant	5/5
MIAT	NR_033319.3	n.2087G>A		non_coding_transcript_exon_variant	4/4
MIAT	NR_033320.3	n.2139G>A		non_coding_transcript_exon_variant	5/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MIAT	ENST00000613780.4	n.2281G>A		non_coding_transcript_exon_variant	5/5	1
MIAT	ENST00000616213.4	n.2081G>A		non_coding_transcript_exon_variant	4/4	1
MIAT	ENST00000616469.4	n.2207G>A		non_coding_transcript_exon_variant	4/4	1

Frequencies

GnomAD3 genomes AF: 0.106 AC: 16092 AN: 152204 Hom.: 972 Cov.: 33

Gnomad AFR AF: 0.0543

Gnomad AMI AF: 0.261

Gnomad AMR AF: 0.0844

Gnomad ASJ AF: 0.129

Gnomad EAS AF: 0.102

Gnomad SAS AF: 0.0828

Gnomad FIN AF: 0.158

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.133

Gnomad OTH AF: 0.0974

GnomAD4 exome AF: 0.124 AC: 30475 AN: 246562 Hom.: 1971 Cov.: 0 AF XY: 0.125 AC XY: 15631 AN XY: 124986

Gnomad4 AFR exome AF: 0.0554

Gnomad4 AMR exome AF: 0.0705

Gnomad4 ASJ exome AF: 0.117

Gnomad4 EAS exome AF: 0.0710

Gnomad4 SAS exome AF: 0.0844

Gnomad4 FIN exome AF: 0.157

Gnomad4 NFE exome AF: 0.134

Gnomad4 OTH exome AF: 0.124

GnomAD4 genome AF: 0.106 AC: 16097 AN: 152322 Hom.: 974 Cov.: 33 AF XY: 0.107 AC XY: 7976 AN XY: 74492

Gnomad4 AFR AF: 0.0541

Gnomad4 AMR AF: 0.0841

Gnomad4 ASJ AF: 0.129

Gnomad4 EAS AF: 0.102

Gnomad4 SAS AF: 0.0837

Gnomad4 FIN AF: 0.158

Gnomad4 NFE AF: 0.133

Gnomad4 OTH AF: 0.0964

Alfa AF: 0.119 Hom.: 136

Bravo AF: 0.0984

Asia WGS AF: 0.0820 AC: 285 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.9
DANN	Benign	0.76

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs34403716; hg19: chr22-27064576;