11-65500727-G-A

Variant names:

• chr11-65500727-G-A
• rs7927113
• ENST00000850956.1:n.1683G>A

Variant summary

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

The ENST00000850956.1(MALAT1):​n.1683G>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 ENST00000850956.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.556
• Publications: 8 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=-0.74).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.118 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000850956.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MALAT1	NR_002819.5	MANE Select	n.1683G>A		non_coding_transcript_exon	Exon 1 of 1
	MALAT1	NR_144567.1		n.2756G>A		non_coding_transcript_exon	Exon 2 of 2
	MALAT1	NR_144568.1		n.2756G>A		non_coding_transcript_exon	Exon 2 of 3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MALAT1	ENST00000850956.1	MANE Select	n.1683G>A		non_coding_transcript_exon	Exon 1 of 1
	MALAT1	ENST00000508832.3	TSL:2	n.1686G>A		non_coding_transcript_exon	Exon 1 of 2
	MALAT1	ENST00000534336.4	TSL:6	n.3122G>A		non_coding_transcript_exon	Exon 1 of 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

GnomAD2 exomes AF: 0.00992 AC: 2300 AN: 231870 AF XY: 0.00807

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 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

African (AFR) AF: 0.130 AC: 1362 AN: 10510

American (AMR) AF: 0.00606 AC: 220 AN: 36302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 11744

East Asian (EAS) AF: 0.00721 AC: 95 AN: 13172

South Asian (SAS) AF: 0.00313 AC: 209 AN: 66766

European-Finnish (FIN) AF: 0.000532 AC: 9 AN: 16916

Middle Eastern (MID) AF: 0.00596 AC: 17 AN: 2852

European-Non Finnish (NFE) AF: 0.000672 AC: 129 AN: 191844

Other (OTH) AF: 0.00969 AC: 161 AN: 16610

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

African (AFR) AF: 0.120 AC: 4999 AN: 41530

American (AMR) AF: 0.0148 AC: 226 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00693 AC: 36 AN: 5194

South Asian (SAS) AF: 0.00228 AC: 11 AN: 4828

European-Finnish (FIN) AF: 0.000282 AC: 3 AN: 10624

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.000941 AC: 64 AN: 68022

Other (OTH) AF: 0.0237 AC: 50 AN: 2108

Alfa AF: 0.0157 Hom.: 50

Bravo AF: 0.0411

Asia WGS AF: 0.0170 AC: 60 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	16
DANN	Benign	0.84
PhyloP100		0.56
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: rs7927113; hg19: chr11-65268198;