rs7927113

Positions:

• chr11-65500727-G-A
• chr11-65500727-G-C

Variant summary

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

The NR_002819.4(MALAT1):​n.2990G>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 0.0147 in 518,992 control chromosomes in the GnomAD database, including 406 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 0.035 (295 hom., cov: 32)
  • Exomes 𝑓: 0.0060 (111 hom.)
• Consequence: MALAT1 NR_002819.4 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.556

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=-0.74).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.118 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MALAT1	NR_002819.4	n.2990G>A		non_coding_transcript_exon_variant	1/1
TALAM1	NR_145459.1	n.6706C>T		non_coding_transcript_exon_variant	1/1
MALAT1	NR_144567.1	n.2756G>A		non_coding_transcript_exon_variant	2/2
MALAT1	NR_144568.1	n.2756G>A		non_coding_transcript_exon_variant	2/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MALAT1	ENST00000534336.3	n.3088G>A		non_coding_transcript_exon_variant	1/1
TALAM1	ENST00000698129.1	n.6706C>T		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes AF: 0.0354 AC: 5390 AN: 152158 Hom.: 294 Cov.: 32

Gnomad AFR AF: 0.120

Gnomad AMI AF: 0.00658

Gnomad AMR AF: 0.0148

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00692

Gnomad SAS AF: 0.00228

Gnomad FIN AF: 0.000282

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.000941

Gnomad OTH AF: 0.0240

GnomAD3 exomes AF: 0.00992 AC: 2300 AN: 231870 Hom.: 124 AF XY: 0.00807 AC XY: 1032 AN XY: 127896

Gnomad AFR exome AF: 0.126

Gnomad AMR exome AF: 0.00632

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00580

Gnomad SAS exome AF: 0.00294

Gnomad FIN exome AF: 0.000515

Gnomad NFE exome AF: 0.000822

Gnomad OTH exome AF: 0.00613

GnomAD4 exome AF: 0.00600 AC: 2202 AN: 366716 Hom.: 111 Cov.: 0 AF XY: 0.00494 AC XY: 1039 AN XY: 210268

Gnomad4 AFR exome AF: 0.130

Gnomad4 AMR exome AF: 0.00606

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00721

Gnomad4 SAS exome AF: 0.00313

Gnomad4 FIN exome AF: 0.000532

Gnomad4 NFE exome AF: 0.000672

Gnomad4 OTH exome AF: 0.00969

GnomAD4 genome AF: 0.0355 AC: 5402 AN: 152276 Hom.: 295 Cov.: 32 AF XY: 0.0350 AC XY: 2606 AN XY: 74468

Gnomad4 AFR AF: 0.120

Gnomad4 AMR AF: 0.0148

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00693

Gnomad4 SAS AF: 0.00228

Gnomad4 FIN AF: 0.000282

Gnomad4 NFE AF: 0.000941

Gnomad4 OTH AF: 0.0237

Alfa AF: 0.0154 Hom.: 27

Bravo AF: 0.0411

Asia WGS AF: 0.0170 AC: 60 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	16
DANN	Benign	0.84
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: rs7927113; hg19: chr11-65268198;