rs619586

Variant names:

• chr11-65498698-A-G
• rs619586
• ENST00000534336.4:n.1093A>G

Your query was ambiguous. Multiple possible variants found:

• chr11-65498698-A-G
• chr11-65498698-A-T

Variant summary

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

The ENST00000534336.4(MALAT1):​n.1093A>G 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 0.0535 in 518,530 control chromosomes in the GnomAD database, including 1,238 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 0.036 (175 hom., cov: 32)
  • Exomes 𝑓: 0.061 (1063 hom.)
• Consequence: MALAT1 ENST00000534336.4 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.183
• Publications: 115 publications found

Genes affected

MALAT1 (HGNC:29665): (metastasis associated lung adenocarcinoma transcript 1) This gene produces a precursor transcript from which a long non-coding RNA is derived by RNase P cleavage of a tRNA-like small ncRNA (known as mascRNA) from its 3' end. The resultant mature transcript lacks a canonical poly(A) tail but is instead stabilized by a 3' triple helical structure. This transcript is retained in the nucleus where it is thought to form molecular scaffolds for ribonucleoprotein complexes. It may act as a transcriptional regulator for numerous genes, including some genes involved in cancer metastasis and cell migration, and it is involved in cell cycle regulation. Its upregulation in multiple cancerous tissues has been associated with the proliferation and metastasis of tumor cells. [provided by RefSeq, Mar 2015]

ENSG00000270117 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.129 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MALAT1	NR_144567.1	n.961A>G		non_coding_transcript_exon_variant	Exon 1 of 2
MALAT1	NR_144568.1	n.961A>G		non_coding_transcript_exon_variant	Exon 1 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MALAT1	ENST00000534336.4	n.1093A>G		non_coding_transcript_exon_variant	Exon 1 of 1	6
ENSG00000270117	ENST00000602344.3	n.207T>C		non_coding_transcript_exon_variant	Exon 1 of 1	6
MALAT1	ENST00000619449.4	n.219A>G		non_coding_transcript_exon_variant	Exon 2 of 3	3

Frequencies

GnomAD3 genomes AF: 0.0356 AC: 5416 AN: 152082 Hom.: 177 Cov.: 32

Gnomad AFR AF: 0.0119

Gnomad AMI AF: 0.00658

Gnomad AMR AF: 0.0535

Gnomad ASJ AF: 0.0138

Gnomad EAS AF: 0.0890

Gnomad SAS AF: 0.138

Gnomad FIN AF: 0.0376

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0358

Gnomad OTH AF: 0.0431

GnomAD2 exomes AF: 0.0593 AC: 13726 AN: 231438 AF XY: 0.0615

Gnomad AFR exome AF: 0.0121

Gnomad AMR exome AF: 0.0860

Gnomad ASJ exome AF: 0.0142

Gnomad EAS exome AF: 0.0841

Gnomad FIN exome AF: 0.0419

Gnomad NFE exome AF: 0.0360

Gnomad OTH exome AF: 0.0452

GnomAD4 exome AF: 0.0610 AC: 22339 AN: 366330 Hom.: 1063 Cov.: 0 AF XY: 0.0662 AC XY: 13900 AN XY: 210066

African (AFR) AF: 0.0124 AC: 130 AN: 10478

American (AMR) AF: 0.0860 AC: 3116 AN: 36232

Ashkenazi Jewish (ASJ) AF: 0.0164 AC: 192 AN: 11734

East Asian (EAS) AF: 0.0824 AC: 1085 AN: 13170

South Asian (SAS) AF: 0.138 AC: 9175 AN: 66704

European-Finnish (FIN) AF: 0.0406 AC: 684 AN: 16846

Middle Eastern (MID) AF: 0.0309 AC: 88 AN: 2850

European-Non Finnish (NFE) AF: 0.0370 AC: 7098 AN: 191726

Other (OTH) AF: 0.0465 AC: 771 AN: 16590

GnomAD4 genome AF: 0.0355 AC: 5410 AN: 152200 Hom.: 175 Cov.: 32 AF XY: 0.0378 AC XY: 2810 AN XY: 74412

African (AFR) AF: 0.0118 AC: 491 AN: 41506

American (AMR) AF: 0.0534 AC: 816 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0138 AC: 48 AN: 3470

East Asian (EAS) AF: 0.0890 AC: 462 AN: 5192

South Asian (SAS) AF: 0.138 AC: 664 AN: 4820

European-Finnish (FIN) AF: 0.0376 AC: 398 AN: 10598

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0358 AC: 2434 AN: 68006

Other (OTH) AF: 0.0427 AC: 90 AN: 2108

Alfa AF: 0.0374 Hom.: 417

Bravo AF: 0.0345

Asia WGS AF: 0.109 AC: 378 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	1.7
DANN	Benign	0.27
PhyloP100		0.18

Splicing

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

Other links and lift over

dbSNP: rs619586; hg19: chr11-65266169;