5-16522016-C-T

Variant names:

• chr5-16522016-C-T
• rs163282
• NM_001034850.3:c.459-38544G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 publications found

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]

RETREG1 Gene-Disease associations (from GenCC):

• neuropathy, hereditary sensory and autonomic, type 2B

  Inheritance: AR Classification: DEFINITIVE Submitted by: G2P
• hereditary sensory and autonomic neuropathy type 2

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
RETREG1	NM_001034850.3	c.459-38544G>A		intron_variant	Intron 3 of 8	ENST00000306320.10	NP_001030022.1
RETREG1	XM_011514053.4	c.459-16493G>A		intron_variant	Intron 3 of 9		XP_011512355.1
RETREG1	XM_011514055.4	c.59+20285G>A		intron_variant	Intron 1 of 6		XP_011512357.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RETREG1	ENST00000306320.10	c.459-38544G>A		intron_variant	Intron 3 of 8	1	NM_001034850.3	ENSP00000304642.9

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

African (AFR) AF: 0.235 AC: 9725 AN: 41436

American (AMR) AF: 0.168 AC: 2573 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.254 AC: 881 AN: 3470

East Asian (EAS) AF: 0.414 AC: 2130 AN: 5146

South Asian (SAS) AF: 0.384 AC: 1847 AN: 4814

European-Finnish (FIN) AF: 0.222 AC: 2342 AN: 10572

Middle Eastern (MID) AF: 0.310 AC: 91 AN: 294

European-Non Finnish (NFE) AF: 0.248 AC: 16867 AN: 67982

Other (OTH) AF: 0.236 AC: 498 AN: 2112

Alfa AF: 0.246 Hom.: 20086

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
PhyloP100		-1.6
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs163282; hg19: chr5-16522125;