22-26670771-T-C

Variant names:

• chr22-26670771-T-C
• rs73163297
• ENST00000613780.4:n.4439T>C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The ENST00000613780.4(MIAT):​n.4439T>C 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 0.00771 in 398,556 control chromosomes in the GnomAD database, including 22 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0069 (10 hom., cov: 31)
  • Exomes 𝑓: 0.0082 (12 hom.)
• Consequence: MIAT ENST00000613780.4 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.105

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]

ENSG00000206028 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 22-26670771-T-C is Benign according to our data. Variant chr22-26670771-T-C is described in ClinVar as [Benign]. Clinvar id is 2653010.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.0082 (2020/246306) while in subpopulation MID AF= 0.0263 (34/1294). AF 95% confidence interval is 0.0193. There are 12 homozygotes in gnomad4_exome. There are 990 alleles in male gnomad4_exome subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 10 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MIAT	NR_003491.4	n.4371T>C		non_coding_transcript_exon_variant	Exon 5 of 5
MIAT	NR_033319.3	n.4245T>C		non_coding_transcript_exon_variant	Exon 4 of 4
MIAT	NR_033320.3	n.4297T>C		non_coding_transcript_exon_variant	Exon 5 of 5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MIAT	ENST00000613780.4	n.4439T>C		non_coding_transcript_exon_variant	Exon 5 of 5	1
MIAT	ENST00000616213.4	n.4239T>C		non_coding_transcript_exon_variant	Exon 4 of 4	1
MIAT	ENST00000616469.4	n.4365T>C		non_coding_transcript_exon_variant	Exon 4 of 4	1

Frequencies

GnomAD3 genomes AF: 0.00692 AC: 1052 AN: 152132 Hom.: 10 Cov.: 31

Gnomad AFR AF: 0.00121

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.0112

Gnomad ASJ AF: 0.0130

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00269

Gnomad FIN AF: 0.0140

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.00879

Gnomad OTH AF: 0.00862

GnomAD4 exome AF: 0.00820 AC: 2020 AN: 246306 Hom.: 12 Cov.: 0 AF XY: 0.00793 AC XY: 990 AN XY: 124800

Gnomad4 AFR exome AF: 0.00139

Gnomad4 AMR exome AF: 0.00511

Gnomad4 ASJ exome AF: 0.0150

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00297

Gnomad4 FIN exome AF: 0.0108

Gnomad4 NFE exome AF: 0.00903

Gnomad4 OTH exome AF: 0.00849

GnomAD4 genome AF: 0.00691 AC: 1052 AN: 152250 Hom.: 10 Cov.: 31 AF XY: 0.00725 AC XY: 540 AN XY: 74450

Gnomad4 AFR AF: 0.00120

Gnomad4 AMR AF: 0.0112

Gnomad4 ASJ AF: 0.0130

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00270

Gnomad4 FIN AF: 0.0140

Gnomad4 NFE AF: 0.00879

Gnomad4 OTH AF: 0.00853

Alfa AF: 0.00773 Hom.: 0

Bravo AF: 0.00631

Asia WGS AF: 0.00115 AC: 5 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

MIAT: BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	5.7
DANN	Benign	0.58

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs73163297; hg19: chr22-27066734;