rs763271

Positions:

• chr22-26647269-C-G

Variant summary

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

The ENST00000643270.1(MIAT):​n.604C>G 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 0.277 in 397,784 control chromosomes in the GnomAD database, including 16,113 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 0.26 (5360 hom., cov: 29)
  • Exomes 𝑓: 0.29 (10753 hom.)
• Consequence: MIAT ENST00000643270.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.131

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.42 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MIAT	ENST00000643270.1	n.604C>G		non_coding_transcript_exon_variant	2/6

Frequencies

GnomAD3 genomes AF: 0.262 AC: 39674 AN: 151406 Hom.: 5360 Cov.: 29

Gnomad AFR AF: 0.208

Gnomad AMI AF: 0.302

Gnomad AMR AF: 0.262

Gnomad ASJ AF: 0.349

Gnomad EAS AF: 0.435

Gnomad SAS AF: 0.373

Gnomad FIN AF: 0.285

Gnomad MID AF: 0.259

Gnomad NFE AF: 0.265

Gnomad OTH AF: 0.277

GnomAD4 exome AF: 0.286 AC: 70501 AN: 246258 Hom.: 10753 Cov.: 0 AF XY: 0.285 AC XY: 35604 AN XY: 124778

Gnomad4 AFR exome AF: 0.211

Gnomad4 AMR exome AF: 0.256

Gnomad4 ASJ exome AF: 0.343

Gnomad4 EAS exome AF: 0.459

Gnomad4 SAS exome AF: 0.369

Gnomad4 FIN exome AF: 0.283

Gnomad4 NFE exome AF: 0.262

Gnomad4 OTH exome AF: 0.282

GnomAD4 genome AF: 0.262 AC: 39688 AN: 151526 Hom.: 5360 Cov.: 29 AF XY: 0.264 AC XY: 19537 AN XY: 74022

Gnomad4 AFR AF: 0.208

Gnomad4 AMR AF: 0.262

Gnomad4 ASJ AF: 0.349

Gnomad4 EAS AF: 0.435

Gnomad4 SAS AF: 0.373

Gnomad4 FIN AF: 0.285

Gnomad4 NFE AF: 0.265

Gnomad4 OTH AF: 0.274

Alfa AF: 0.254 Hom.: 603

Bravo AF: 0.257

Asia WGS AF: 0.365 AC: 1271 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	2.2
DANN	Benign	0.49

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs763271; hg19: chr22-27043233;