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 ENST00000619449.3(MALAT1):​n.195A>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 ENST00000619449.3 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.183

Genes affected

MALAT1 (HGNC:):

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	Protein	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	Protein	Appris	UniProt
MALAT1	ENST00000534336.3	n.1059A>G		non_coding_transcript_exon_variant	1/1	6
MALAT1	ENST00000619449.3	n.195A>G		non_coding_transcript_exon_variant	2/3	3
MALAT1	ENST00000710855.1	n.311A>G		non_coding_transcript_exon_variant	1/2

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;