22-26666332-G-A

Variant names:

• chr22-26666332-G-A
• rs62224896
• ENST00000620145.6:n.952G>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.1094G>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 0.116 in 398,502 control chromosomes in the GnomAD database, including 2,918 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.11 (960 hom., cov: 32)
  • Exomes 𝑓: 0.12 (1958 hom.)
• Consequence: MIAT ENST00000613780.4 non_coding_transcript_exon
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: -0.716
• Publications: 7 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=-0.9).
• BP6: Variant 22-26666332-G-A is Benign according to our data. Variant chr22-26666332-G-A is described in ClinVar as Benign. ClinVar VariationId is 2691795.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.13 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.952G>A		non_coding_transcript_exon	Exon 3 of 5
	MIAT	NR_003491.4		n.1026G>A		non_coding_transcript_exon	Exon 3 of 5
	MIAT	NR_033319.3		n.1026G>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.952G>A		non_coding_transcript_exon	Exon 3 of 5
	MIAT	ENST00000613780.4	TSL:1	n.1094G>A		non_coding_transcript_exon	Exon 3 of 5
	MIAT	ENST00000616213.4	TSL:1	n.1020G>A		non_coding_transcript_exon	Exon 3 of 4

Frequencies

GnomAD3 genomes AF: 0.105 AC: 16016 AN: 152036 Hom.: 958 Cov.: 32

Gnomad AFR AF: 0.0543

Gnomad AMI AF: 0.260

Gnomad AMR AF: 0.0859

Gnomad ASJ AF: 0.129

Gnomad EAS AF: 0.101

Gnomad SAS AF: 0.0790

Gnomad FIN AF: 0.155

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.132

Gnomad OTH AF: 0.0977

GnomAD4 exome AF: 0.123 AC: 30239 AN: 246348 Hom.: 1958 Cov.: 0 AF XY: 0.124 AC XY: 15520 AN XY: 124830

African (AFR) AF: 0.0557 AC: 400 AN: 7182

American (AMR) AF: 0.0720 AC: 535 AN: 7434

Ashkenazi Jewish (ASJ) AF: 0.117 AC: 1078 AN: 9240

East Asian (EAS) AF: 0.0669 AC: 1531 AN: 22894

South Asian (SAS) AF: 0.0782 AC: 237 AN: 3030

European-Finnish (FIN) AF: 0.155 AC: 3232 AN: 20832

Middle Eastern (MID) AF: 0.127 AC: 165 AN: 1296

European-Non Finnish (NFE) AF: 0.133 AC: 21036 AN: 158068

Other (OTH) AF: 0.124 AC: 2025 AN: 16372

GnomAD4 genome AF: 0.105 AC: 16021 AN: 152154 Hom.: 960 Cov.: 32 AF XY: 0.107 AC XY: 7928 AN XY: 74396

African (AFR) AF: 0.0541 AC: 2247 AN: 41504

American (AMR) AF: 0.0857 AC: 1311 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.129 AC: 447 AN: 3468

East Asian (EAS) AF: 0.101 AC: 522 AN: 5176

South Asian (SAS) AF: 0.0799 AC: 386 AN: 4832

European-Finnish (FIN) AF: 0.155 AC: 1643 AN: 10592

Middle Eastern (MID) AF: 0.129 AC: 38 AN: 294

European-Non Finnish (NFE) AF: 0.132 AC: 8986 AN: 67968

Other (OTH) AF: 0.0967 AC: 204 AN: 2110

Alfa AF: 0.117 Hom.: 170

Bravo AF: 0.0987

Asia WGS AF: 0.0790 AC: 275 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	-0.90
CADD	Benign	0.42
DANN	Benign	0.52
PhyloP100		-0.72
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: rs62224896; hg19: chr22-27062296;