11-65501878-C-G

Variant names:

• chr11-65501878-C-G
• rs664589
• ENST00000850956.1:n.2834C>G

Variant summary

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

The ENST00000850956.1(MALAT1):​n.2834C>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 ENST00000850956.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.285
• Publications: 41 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]

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

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
MALAT1	NR_002819.5	n.2834C>G		non_coding_transcript_exon_variant	Exon 1 of 1	ENST00000850956.1
MALAT1	NR_144567.1	n.3907C>G		non_coding_transcript_exon_variant	Exon 2 of 2
MALAT1	NR_144568.1	n.3907C>G		non_coding_transcript_exon_variant	Exon 2 of 3
TALAM1	NR_145459.1	n.5555G>C		non_coding_transcript_exon_variant	Exon 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MALAT1	ENST00000850956.1	n.2834C>G		non_coding_transcript_exon_variant	Exon 1 of 1		NR_002819.5

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

GnomAD2 exomes AF: 0.0601 AC: 13702 AN: 228018 AF XY: 0.0624

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 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

African (AFR) AF: 0.0251 AC: 263 AN: 10496

American (AMR) AF: 0.0860 AC: 3079 AN: 35786

Ashkenazi Jewish (ASJ) AF: 0.0162 AC: 190 AN: 11694

East Asian (EAS) AF: 0.0777 AC: 1022 AN: 13150

South Asian (SAS) AF: 0.137 AC: 9121 AN: 66578

European-Finnish (FIN) AF: 0.0405 AC: 683 AN: 16870

Middle Eastern (MID) AF: 0.0319 AC: 91 AN: 2852

European-Non Finnish (NFE) AF: 0.0382 AC: 7284 AN: 190900

Other (OTH) AF: 0.0465 AC: 769 AN: 16542

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

African (AFR) AF: 0.0240 AC: 994 AN: 41492

American (AMR) AF: 0.0549 AC: 839 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.0136 AC: 47 AN: 3466

East Asian (EAS) AF: 0.0826 AC: 428 AN: 5184

South Asian (SAS) AF: 0.138 AC: 666 AN: 4812

European-Finnish (FIN) AF: 0.0373 AC: 395 AN: 10588

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

European-Non Finnish (NFE) AF: 0.0375 AC: 2547 AN: 67996

Other (OTH) AF: 0.0464 AC: 98 AN: 2110

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
PhyloP100		-0.28
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

Other links and lift over

dbSNP: rs664589; hg19: chr11-65269349;