rs2331291

Variant names:

• chr22-26662857-C-T
• rs2331291
• ENST00000613780.4:n.136-459C>T

Variant summary

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

The ENST00000613780.4(MIAT):​n.136-459C>T variant causes a intron 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. Variant has been reported in ClinVar as no classification for the single variant (no stars).

• Frequency: Genomes: 𝑓 0.11 (1053 hom., cov: 32)
• Consequence: MIAT ENST00000613780.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.228
• Publications: 15 publications found

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]

MIATNB (HGNC:50731): (MIAT neighbor)

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
MIAT	NR_003491.4	n.68-459C>T		intron_variant	Intron 1 of 4
MIAT	NR_033319.3	n.68-459C>T		intron_variant	Intron 1 of 3
MIAT	NR_033320.3	n.68-459C>T		intron_variant	Intron 1 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MIAT	ENST00000613780.4	n.136-459C>T		intron_variant	Intron 1 of 4	1
MIAT	ENST00000616213.4	n.136-459C>T		intron_variant	Intron 1 of 3	1
MIAT	ENST00000616469.4	n.188-459C>T		intron_variant	Intron 1 of 3	1

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

African (AFR) AF: 0.0487 AC: 2021 AN: 41490

American (AMR) AF: 0.0851 AC: 1300 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.129 AC: 448 AN: 3470

East Asian (EAS) AF: 0.105 AC: 542 AN: 5172

South Asian (SAS) AF: 0.0832 AC: 401 AN: 4818

European-Finnish (FIN) AF: 0.180 AC: 1901 AN: 10554

Middle Eastern (MID) AF: 0.133 AC: 39 AN: 294

European-Non Finnish (NFE) AF: 0.138 AC: 9396 AN: 67964

Other (OTH) AF: 0.0992 AC: 210 AN: 2116

Alfa AF: 0.116 Hom.: 1604

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
PhyloP100		0.23
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs2331291; hg19: chr22-27058821;