rs664589

Positions:

• chr11-65501878-C-G
• chr11-65501878-C-T

Variant summary

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

The NR_002819.4(MALAT1):​n.4141C>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 0.0552 in 516,998 control chromosomes in the GnomAD database, including 1,247 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 0.040 (185 hom., cov: 32)
  • Exomes 𝑓: 0.062 (1062 hom.)
• Consequence: MALAT1 NR_002819.4 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.285

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]

TALAM1 (HGNC:54476): (TALAM1 transcript, MALAT1 antisense RNA)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.13 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MALAT1	NR_002819.4	n.4141C>G		non_coding_transcript_exon_variant	1/1
TALAM1	NR_145459.1	n.5555G>C		non_coding_transcript_exon_variant	1/1
MALAT1	NR_144567.1	n.3907C>G		non_coding_transcript_exon_variant	2/2
MALAT1	NR_144568.1	n.3907C>G		non_coding_transcript_exon_variant	2/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MALAT1	ENST00000534336.3	n.4239C>G		non_coding_transcript_exon_variant	1/1
TALAM1	ENST00000698129.1	n.5555G>C		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes AF: 0.0396 AC: 6017 AN: 152012 Hom.: 186 Cov.: 32

Gnomad AFR AF: 0.0238

Gnomad AMI AF: 0.00658

Gnomad AMR AF: 0.0551

Gnomad ASJ AF: 0.0136

Gnomad EAS AF: 0.0824

Gnomad SAS AF: 0.139

Gnomad FIN AF: 0.0373

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0375

Gnomad OTH AF: 0.0469

GnomAD3 exomes AF: 0.0601 AC: 13702 AN: 228018 Hom.: 616 AF XY: 0.0624 AC XY: 7844 AN XY: 125804

Gnomad AFR exome AF: 0.0236

Gnomad AMR exome AF: 0.0858

Gnomad ASJ exome AF: 0.0142

Gnomad EAS exome AF: 0.0790

Gnomad SAS exome AF: 0.143

Gnomad FIN exome AF: 0.0416

Gnomad NFE exome AF: 0.0371

Gnomad OTH exome AF: 0.0469

GnomAD4 exome AF: 0.0617 AC: 22502 AN: 364868 Hom.: 1062 Cov.: 0 AF XY: 0.0667 AC XY: 13962 AN XY: 209174

Gnomad4 AFR exome AF: 0.0251

Gnomad4 AMR exome AF: 0.0860

Gnomad4 ASJ exome AF: 0.0162

Gnomad4 EAS exome AF: 0.0777

Gnomad4 SAS exome AF: 0.137

Gnomad4 FIN exome AF: 0.0405

Gnomad4 NFE exome AF: 0.0382

Gnomad4 OTH exome AF: 0.0465

GnomAD4 genome AF: 0.0396 AC: 6021 AN: 152130 Hom.: 185 Cov.: 32 AF XY: 0.0415 AC XY: 3087 AN XY: 74362

Gnomad4 AFR AF: 0.0240

Gnomad4 AMR AF: 0.0549

Gnomad4 ASJ AF: 0.0136

Gnomad4 EAS AF: 0.0826

Gnomad4 SAS AF: 0.138

Gnomad4 FIN AF: 0.0373

Gnomad4 NFE AF: 0.0375

Gnomad4 OTH AF: 0.0464

Alfa AF: 0.0331 Hom.: 15

Bravo AF: 0.0389

Asia WGS AF: 0.0950 AC: 329 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	11
DANN	Benign	0.82
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs664589; hg19: chr11-65269349;