16-86483494-T-G

Variant names:

• chr16-86483494-T-G
• rs4843966
• ENST00000595886.1:n.207-4738A>C

Variant summary

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

The ENST00000595886.1(FENDRR):​n.207-4738A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.103 in 152,306 control chromosomes in the GnomAD database, including 1,041 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 0.10 (1041 hom., cov: 33)
• Consequence: FENDRR ENST00000595886.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.490
• Publications: 2 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.202 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FENDRR	NR_033925.1	n.207-4738A>C		intron_variant	Intron 1 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FENDRR	ENST00000595886.1	n.207-4738A>C		intron_variant	Intron 1 of 3	2
FENDRR	ENST00000600553.5	n.280-6295A>C		intron_variant	Intron 2 of 2	3
FENDRR	ENST00000659025.1	n.798-5362A>C		intron_variant	Intron 3 of 4

Frequencies

GnomAD3 genomes AF: 0.103 AC: 15703 AN: 152186 Hom.: 1027 Cov.: 33

Gnomad AFR AF: 0.0385

Gnomad AMI AF: 0.0450

Gnomad AMR AF: 0.207

Gnomad ASJ AF: 0.129

Gnomad EAS AF: 0.149

Gnomad SAS AF: 0.137

Gnomad FIN AF: 0.0834

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.115

Gnomad OTH AF: 0.120

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

GnomAD4 genome AF: 0.103 AC: 15737 AN: 152306 Hom.: 1041 Cov.: 33 AF XY: 0.104 AC XY: 7770 AN XY: 74472

African (AFR) AF: 0.0384 AC: 1598 AN: 41570

American (AMR) AF: 0.208 AC: 3180 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.129 AC: 449 AN: 3472

East Asian (EAS) AF: 0.149 AC: 771 AN: 5184

South Asian (SAS) AF: 0.136 AC: 658 AN: 4828

European-Finnish (FIN) AF: 0.0834 AC: 885 AN: 10616

Middle Eastern (MID) AF: 0.102 AC: 30 AN: 294

European-Non Finnish (NFE) AF: 0.116 AC: 7857 AN: 68022

Other (OTH) AF: 0.127 AC: 268 AN: 2112

Alfa AF: 0.118 Hom.: 1986

Bravo AF: 0.112

Asia WGS AF: 0.163 AC: 570 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.1
DANN	Benign	0.44
PhyloP100		0.49

Splicing

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

Other links and lift over

dbSNP: rs4843966; hg19: chr16-86517100;