rs2331291

Positions:

• chr22-26662857-C-T

Variant summary

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

The NR_003491.3(MIAT):​n.174-459C>T variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.108 in 152,068 control chromosomes in the GnomAD database, including 1,053 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 (1053 hom., cov: 32)
• Consequence: MIAT NR_003491.3 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.228

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=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.136 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MIAT	NR_003491.3	n.174-459C>T		intron_variant, non_coding_transcript_variant
MIAT	NR_033319.2	n.174-459C>T		intron_variant, non_coding_transcript_variant
MIAT	NR_033320.2	n.174-459C>T		intron_variant, non_coding_transcript_variant
MIAT	NR_033321.2	n.174-459C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MIAT	ENST00000643270.1	n.647-459C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.109 AC: 16490 AN: 151950 Hom.: 1051 Cov.: 32

Gnomad AFR AF: 0.0488

Gnomad AMI AF: 0.262

Gnomad AMR AF: 0.0853

Gnomad ASJ AF: 0.129

Gnomad EAS AF: 0.105

Gnomad SAS AF: 0.0823

Gnomad FIN AF: 0.180

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.138

Gnomad OTH AF: 0.100

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

GnomAD4 genome AF: 0.108 AC: 16496 AN: 152068 Hom.: 1053 Cov.: 32 AF XY: 0.111 AC XY: 8247 AN XY: 74338

Gnomad4 AFR AF: 0.0487

Gnomad4 AMR AF: 0.0851

Gnomad4 ASJ AF: 0.129

Gnomad4 EAS AF: 0.105

Gnomad4 SAS AF: 0.0832

Gnomad4 FIN AF: 0.180

Gnomad4 NFE AF: 0.138

Gnomad4 OTH AF: 0.0992

Alfa AF: 0.127 Hom.: 1170

Bravo AF: 0.0992

Asia WGS AF: 0.0860 AC: 299 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	4.0
DANN	Benign	0.92

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2331291; hg19: chr22-27058821;