rs4274

Variant names:

• chr22-26668324-G-A
• rs4274
• ENST00000613780.4:n.1992G>A

Variant summary

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

The ENST00000613780.4(MIAT):​n.1992G>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 0.163 in 398,450 control chromosomes in the GnomAD database, including 6,313 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 0.15 (2021 hom., cov: 32)
  • Exomes 𝑓: 0.17 (4292 hom.)
• Consequence: MIAT ENST00000613780.4 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.984

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.37 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MIAT	NR_003491.4	n.1924G>A		non_coding_transcript_exon_variant	Exon 5 of 5
MIAT	NR_033319.3	n.1798G>A		non_coding_transcript_exon_variant	Exon 4 of 4
MIAT	NR_033320.3	n.1850G>A		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.1992G>A		non_coding_transcript_exon_variant	Exon 5 of 5	1
MIAT	ENST00000616213.4	n.1792G>A		non_coding_transcript_exon_variant	Exon 4 of 4	1
MIAT	ENST00000616469.4	n.1918G>A		non_coding_transcript_exon_variant	Exon 4 of 4	1

Frequencies

GnomAD3 genomes AF: 0.151 AC: 22905 AN: 151978 Hom.: 2016 Cov.: 32

Gnomad AFR AF: 0.111

Gnomad AMI AF: 0.159

Gnomad AMR AF: 0.184

Gnomad ASJ AF: 0.177

Gnomad EAS AF: 0.383

Gnomad SAS AF: 0.254

Gnomad FIN AF: 0.105

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.148

Gnomad OTH AF: 0.175

GnomAD4 exome AF: 0.171 AC: 42034 AN: 246354 Hom.: 4292 Cov.: 0 AF XY: 0.169 AC XY: 21142 AN XY: 124830

Gnomad4 AFR exome AF: 0.114

Gnomad4 AMR exome AF: 0.193

Gnomad4 ASJ exome AF: 0.180

Gnomad4 EAS exome AF: 0.399

Gnomad4 SAS exome AF: 0.244

Gnomad4 FIN exome AF: 0.114

Gnomad4 NFE exome AF: 0.144

Gnomad4 OTH exome AF: 0.171

GnomAD4 genome AF: 0.151 AC: 22922 AN: 152096 Hom.: 2021 Cov.: 32 AF XY: 0.151 AC XY: 11208 AN XY: 74348

Gnomad4 AFR AF: 0.111

Gnomad4 AMR AF: 0.184

Gnomad4 ASJ AF: 0.177

Gnomad4 EAS AF: 0.384

Gnomad4 SAS AF: 0.254

Gnomad4 FIN AF: 0.105

Gnomad4 NFE AF: 0.148

Gnomad4 OTH AF: 0.175

Alfa AF: 0.151 Hom.: 3101

Bravo AF: 0.154

Asia WGS AF: 0.269 AC: 932 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	7.1
DANN	Benign	0.74

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4274; hg19: chr22-27064287;