16-86481593-G-T

Position:

• chr16-86481593-G-T

Variant summary

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

The NR_033925.1(FENDRR):​n.207-2837C>A variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.396 in 152,146 control chromosomes in the GnomAD database, including 13,142 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 0.40 (13142 hom., cov: 33)
• Consequence: FENDRR NR_033925.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.944

Genes affected

FENDRR (HGNC:43894): (FOXF1 adjacent non-coding developmental regulatory RNA) This gene produces a spliced long non-coding RNA transcribed bidirectionally with FOXF1 on the opposite strand. A similar gene in mouse is essential for normal development of the heart and body wall. The encoded transcript is thought to act by binding to polycomb repressive complex 2 (PRC2) and/or TrxG/MLL complexes to promote the methylation of the promoters of target genes, thus reducing their expression. It has been suggested that this transcript may play a role in the progression of gastric cancer. Alternatively spliced transcript variants have been identified. [provided by RefSeq, Mar 2015]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.489 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FENDRR	NR_033925.1	n.207-2837C>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FENDRR	ENST00000659025.1	n.798-3461C>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.397 AC: 60309 AN: 152028 Hom.: 13152 Cov.: 33

Gnomad AFR AF: 0.208

Gnomad AMI AF: 0.466

Gnomad AMR AF: 0.403

Gnomad ASJ AF: 0.415

Gnomad EAS AF: 0.387

Gnomad SAS AF: 0.404

Gnomad FIN AF: 0.487

Gnomad MID AF: 0.427

Gnomad NFE AF: 0.493

Gnomad OTH AF: 0.428

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.396 AC: 60303 AN: 152146 Hom.: 13142 Cov.: 33 AF XY: 0.396 AC XY: 29483 AN XY: 74374

Gnomad4 AFR AF: 0.208

Gnomad4 AMR AF: 0.403

Gnomad4 ASJ AF: 0.415

Gnomad4 EAS AF: 0.386

Gnomad4 SAS AF: 0.402

Gnomad4 FIN AF: 0.487

Gnomad4 NFE AF: 0.493

Gnomad4 OTH AF: 0.426

Alfa AF: 0.466 Hom.: 27139

Bravo AF: 0.382

Asia WGS AF: 0.374 AC: 1299 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.29
DANN	Benign	0.52

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs889593; hg19: chr16-86515199;