rs619586

Positions:

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

Variant summary

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

The NR_002819.4(MALAT1):​n.961A>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 NR_002819.4 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.183

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
MALAT1	NR_002819.4	n.961A>G		non_coding_transcript_exon_variant	1/1
MALAT1	NR_144567.1	n.961A>G		non_coding_transcript_exon_variant	1/2
MALAT1	NR_144568.1	n.961A>G		non_coding_transcript_exon_variant	1/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MALAT1	ENST00000534336.3	n.1059A>G		non_coding_transcript_exon_variant	1/1

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

GnomAD3 exomes AF: 0.0593 AC: 13726 AN: 231438 Hom.: 637 AF XY: 0.0615 AC XY: 7852 AN XY: 127680

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 SAS exome AF: 0.144

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

Gnomad4 AFR exome AF: 0.0124

Gnomad4 AMR exome AF: 0.0860

Gnomad4 ASJ exome AF: 0.0164

Gnomad4 EAS exome AF: 0.0824

Gnomad4 SAS exome AF: 0.138

Gnomad4 FIN exome AF: 0.0406

Gnomad4 NFE exome AF: 0.0370

Gnomad4 OTH exome AF: 0.0465

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

Gnomad4 AFR AF: 0.0118

Gnomad4 AMR AF: 0.0534

Gnomad4 ASJ AF: 0.0138

Gnomad4 EAS AF: 0.0890

Gnomad4 SAS AF: 0.138

Gnomad4 FIN AF: 0.0376

Gnomad4 NFE AF: 0.0358

Gnomad4 OTH AF: 0.0427

Alfa AF: 0.0384 Hom.: 213

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs619586; hg19: chr11-65266169;