rs163282

chr5-16522016-C-T

Variant summary

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

The NM_001034850.3(RETREG1):c.459-38544G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.244 in 152,024 control chromosomes in the GnomAD database, including 4,774 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 0.24 (4774 hom., cov: 32)
• Consequence: RETREG1 NM_001034850.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.64

Genes affected

RETREG1 (HGNC:25964): (reticulophagy regulator 1) The protein encoded by this gene is a cis-Golgi transmembrane protein that may be necessary for the long-term survival of nociceptive and autonomic ganglion neurons. Mutations in this gene are a cause of hereditary sensory and autonomic neuropathy type IIB (HSAN IIB), and this gene may also play a role in susceptibility to vascular dementia. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Nov 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.399 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RETREG1	NM_001034850.3	c.459-38544G>A		intron_variant		ENST00000306320.10
RETREG1	XM_011514053.4	c.459-16493G>A		intron_variant
RETREG1	XM_011514055.4	c.59+20285G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RETREG1	ENST00000306320.10	c.459-38544G>A		intron_variant		1	NM_001034850.3

Frequencies

GnomAD3 genomes AF: 0.244 AC: 37121 AN: 151906 Hom.: 4769 Cov.: 32

Gnomad AFR AF: 0.235

Gnomad AMI AF: 0.201

Gnomad AMR AF: 0.169

Gnomad ASJ AF: 0.254

Gnomad EAS AF: 0.415

Gnomad SAS AF: 0.383

Gnomad FIN AF: 0.222

Gnomad MID AF: 0.297

Gnomad NFE AF: 0.248

Gnomad OTH AF: 0.230

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

GnomAD4 genome AF: 0.244 AC: 37137 AN: 152024 Hom.: 4774 Cov.: 32 AF XY: 0.243 AC XY: 18083 AN XY: 74304

Gnomad4 AFR AF: 0.235

Gnomad4 AMR AF: 0.168

Gnomad4 ASJ AF: 0.254

Gnomad4 EAS AF: 0.414

Gnomad4 SAS AF: 0.384

Gnomad4 FIN AF: 0.222

Gnomad4 NFE AF: 0.248

Gnomad4 OTH AF: 0.236

Alfa AF: 0.245 Hom.: 9739

Bravo AF: 0.235

Asia WGS AF: 0.382 AC: 1327 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	0.21
Dann	Benign	0.51

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: rs163282; hg19: chr5-16522125;