rs3200401

Variant names:

• chr11-65504361-C-T
• rs3200401
• ENST00000850956.1:n.5317C>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The ENST00000612781.2(MALAT1):​n.1211+3C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.171 in 516,094 control chromosomes in the GnomAD database, including 8,189 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 0.17 (2317 hom., cov: 31)
  • Exomes 𝑓: 0.17 (5872 hom.)
• Consequence: MALAT1 ENST00000612781.2 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.56
• Publications: 108 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.3).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.203 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000612781.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MALAT1	NR_002819.5	MANE Select	n.5317C>T		non_coding_transcript_exon	Exon 1 of 1
	MALAT1	NR_144567.1		n.6390C>T		non_coding_transcript_exon	Exon 2 of 2
	MALAT1	NR_144568.1		n.6147C>T		non_coding_transcript_exon	Exon 3 of 3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MALAT1	ENST00000850956.1	MANE Select	n.5317C>T		non_coding_transcript_exon	Exon 1 of 1
	MALAT1	ENST00000508832.3	TSL:2	n.5077C>T		non_coding_transcript_exon	Exon 2 of 2
	MALAT1	ENST00000534336.4	TSL:6	n.6756C>T		non_coding_transcript_exon	Exon 1 of 1

Frequencies

GnomAD3 genomes AF: 0.168 AC: 25322 AN: 150644 Hom.: 2317 Cov.: 31

Gnomad AFR AF: 0.132

Gnomad AMI AF: 0.314

Gnomad AMR AF: 0.149

Gnomad ASJ AF: 0.187

Gnomad EAS AF: 0.170

Gnomad SAS AF: 0.113

Gnomad FIN AF: 0.0915

Gnomad MID AF: 0.268

Gnomad NFE AF: 0.206

Gnomad OTH AF: 0.167

GnomAD2 exomes AF: 0.167 AC: 38316 AN: 229680 AF XY: 0.167

Gnomad AFR exome AF: 0.131

Gnomad AMR exome AF: 0.134

Gnomad ASJ exome AF: 0.178

Gnomad EAS exome AF: 0.161

Gnomad FIN exome AF: 0.0993

Gnomad NFE exome AF: 0.202

Gnomad OTH exome AF: 0.186

GnomAD4 exome AF: 0.172 AC: 62670 AN: 365332 Hom.: 5872 Cov.: 0 AF XY: 0.170 AC XY: 35668 AN XY: 209448

African (AFR) AF: 0.133 AC: 1389 AN: 10472

American (AMR) AF: 0.135 AC: 4878 AN: 36064

Ashkenazi Jewish (ASJ) AF: 0.182 AC: 2127 AN: 11712

East Asian (EAS) AF: 0.157 AC: 2069 AN: 13164

South Asian (SAS) AF: 0.123 AC: 8140 AN: 66412

European-Finnish (FIN) AF: 0.102 AC: 1723 AN: 16884

Middle Eastern (MID) AF: 0.288 AC: 821 AN: 2850

European-Non Finnish (NFE) AF: 0.202 AC: 38562 AN: 191208

Other (OTH) AF: 0.179 AC: 2961 AN: 16566

GnomAD4 genome AF: 0.168 AC: 25325 AN: 150762 Hom.: 2317 Cov.: 31 AF XY: 0.160 AC XY: 11763 AN XY: 73486

African (AFR) AF: 0.132 AC: 5414 AN: 40986

American (AMR) AF: 0.149 AC: 2253 AN: 15132

Ashkenazi Jewish (ASJ) AF: 0.187 AC: 646 AN: 3458

East Asian (EAS) AF: 0.171 AC: 875 AN: 5130

South Asian (SAS) AF: 0.113 AC: 540 AN: 4784

European-Finnish (FIN) AF: 0.0915 AC: 936 AN: 10224

Middle Eastern (MID) AF: 0.260 AC: 76 AN: 292

European-Non Finnish (NFE) AF: 0.206 AC: 13957 AN: 67750

Other (OTH) AF: 0.163 AC: 342 AN: 2094

Alfa AF: 0.194 Hom.: 3965

Bravo AF: 0.175

Asia WGS AF: 0.125 AC: 437 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.30
CADD	Benign	19
DANN	Benign	0.94
PhyloP100		2.6

Splicing

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

Other links and lift over

dbSNP: rs3200401; hg19: chr11-65271832; COSMIC: COSV73174580;