rs469727

Positions:

• chr5-112907271-C-T

Variant summary

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

The NM_005669.5(REEP5):​c.213-4753G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.37 in 151,986 control chromosomes in the GnomAD database, including 10,829 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 0.37 (10829 hom., cov: 32)
• Consequence: REEP5 NM_005669.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.260

Genes affected

REEP5 (HGNC:30077): (receptor accessory protein 5) Predicted to be involved in endoplasmic reticulum organization and regulation of intracellular transport. Located in endoplasmic reticulum tubular network. [provided by Alliance of Genome Resources, Apr 2022]

REEP5 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.467 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
REEP5	NM_005669.5	c.213-4753G>A		intron_variant		ENST00000379638.9	NP_005660.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
REEP5	ENST00000379638.9	c.213-4753G>A		intron_variant		1	NM_005669.5	ENSP00000368959.4

Frequencies

GnomAD3 genomes AF: 0.370 AC: 56188 AN: 151868 Hom.: 10804 Cov.: 32

Gnomad AFR AF: 0.472

Gnomad AMI AF: 0.322

Gnomad AMR AF: 0.317

Gnomad ASJ AF: 0.407

Gnomad EAS AF: 0.166

Gnomad SAS AF: 0.246

Gnomad FIN AF: 0.371

Gnomad MID AF: 0.351

Gnomad NFE AF: 0.343

Gnomad OTH AF: 0.355

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

GnomAD4 genome AF: 0.370 AC: 56276 AN: 151986 Hom.: 10829 Cov.: 32 AF XY: 0.367 AC XY: 27258 AN XY: 74292

Gnomad4 AFR AF: 0.473

Gnomad4 AMR AF: 0.317

Gnomad4 ASJ AF: 0.407

Gnomad4 EAS AF: 0.166

Gnomad4 SAS AF: 0.246

Gnomad4 FIN AF: 0.371

Gnomad4 NFE AF: 0.343

Gnomad4 OTH AF: 0.359

Alfa AF: 0.337 Hom.: 11201

Bravo AF: 0.368

Asia WGS AF: 0.233 AC: 815 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	7.8
DANN	Benign	0.70

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs469727; hg19: chr5-112242968; COSMIC: COSV54841188;