rs2301523

Variant names:

• chr22-26666705-G-A
• rs2301523
• ENST00000620145.6:n.1325G>A

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The ENST00000613780.4(MIAT):​n.1467G>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 0.134 in 398,554 control chromosomes in the GnomAD database, including 3,795 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.14 (1665 hom., cov: 32)
  • Exomes 𝑓: 0.13 (2130 hom.)
• Consequence: MIAT ENST00000613780.4 non_coding_transcript_exon
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.0440
• Publications: 22 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 22-26666705-G-A is Benign according to our data. Variant chr22-26666705-G-A is described in ClinVar as Benign. ClinVar VariationId is 2691796.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.18 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000613780.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MIAT	NR_033320.3	MANE Select	n.1325G>A		non_coding_transcript_exon	Exon 3 of 5
	MIAT	NR_003491.4		n.1399G>A		non_coding_transcript_exon	Exon 3 of 5
	MIAT	NR_033319.3		n.1399G>A		non_coding_transcript_exon	Exon 3 of 4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MIAT	ENST00000620145.6	TSL:1 MANE Select	n.1325G>A		non_coding_transcript_exon	Exon 3 of 5
	MIAT	ENST00000613780.4	TSL:1	n.1467G>A		non_coding_transcript_exon	Exon 3 of 5
	MIAT	ENST00000616213.4	TSL:1	n.1393G>A		non_coding_transcript_exon	Exon 3 of 4

Frequencies

GnomAD3 genomes AF: 0.143 AC: 21723 AN: 152076 Hom.: 1661 Cov.: 32

Gnomad AFR AF: 0.184

Gnomad AMI AF: 0.261

Gnomad AMR AF: 0.0951

Gnomad ASJ AF: 0.132

Gnomad EAS AF: 0.103

Gnomad SAS AF: 0.0820

Gnomad FIN AF: 0.158

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.133

Gnomad OTH AF: 0.125

GnomAD4 exome AF: 0.129 AC: 31742 AN: 246360 Hom.: 2130 Cov.: 0 AF XY: 0.130 AC XY: 16198 AN XY: 124840

African (AFR) AF: 0.179 AC: 1284 AN: 7182

American (AMR) AF: 0.0817 AC: 607 AN: 7434

Ashkenazi Jewish (ASJ) AF: 0.120 AC: 1109 AN: 9242

East Asian (EAS) AF: 0.0707 AC: 1620 AN: 22898

South Asian (SAS) AF: 0.0818 AC: 248 AN: 3032

European-Finnish (FIN) AF: 0.157 AC: 3262 AN: 20824

Middle Eastern (MID) AF: 0.138 AC: 179 AN: 1294

European-Non Finnish (NFE) AF: 0.134 AC: 21194 AN: 158078

Other (OTH) AF: 0.137 AC: 2239 AN: 16376

GnomAD4 genome AF: 0.143 AC: 21744 AN: 152194 Hom.: 1665 Cov.: 32 AF XY: 0.143 AC XY: 10650 AN XY: 74412

African (AFR) AF: 0.184 AC: 7619 AN: 41498

American (AMR) AF: 0.0948 AC: 1450 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.132 AC: 460 AN: 3472

East Asian (EAS) AF: 0.102 AC: 531 AN: 5184

South Asian (SAS) AF: 0.0827 AC: 399 AN: 4826

European-Finnish (FIN) AF: 0.158 AC: 1672 AN: 10596

Middle Eastern (MID) AF: 0.146 AC: 43 AN: 294

European-Non Finnish (NFE) AF: 0.133 AC: 9070 AN: 68006

Other (OTH) AF: 0.124 AC: 262 AN: 2112

Alfa AF: 0.134 Hom.: 941

Bravo AF: 0.141

Asia WGS AF: 0.0880 AC: 305 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	MIAT-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.8
DANN	Benign	0.68
PhyloP100		0.044

Splicing

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

Other links and lift over

dbSNP: rs2301523; hg19: chr22-27062669;