rs163281

Positions:

• chr5-16516669-C-A
• chr5-16516669-C-G

Variant summary

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

The NM_001034850.3(RETREG1):​c.459-33197G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.266 in 152,064 control chromosomes in the GnomAD database, including 5,710 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 0.27 (5710 hom., cov: 32)
• Consequence: RETREG1 NM_001034850.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.212

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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.38 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RETREG1	NM_001034850.3	c.459-33197G>T		intron_variant		ENST00000306320.10	NP_001030022.1
RETREG1	XM_011514053.4	c.459-11146G>T		intron_variant			XP_011512355.1
RETREG1	XM_011514055.4	c.59+25632G>T		intron_variant			XP_011512357.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RETREG1	ENST00000306320.10	c.459-33197G>T		intron_variant		1	NM_001034850.3	ENSP00000304642

Frequencies

GnomAD3 genomes AF: 0.266 AC: 40388 AN: 151946 Hom.: 5705 Cov.: 32

Gnomad AFR AF: 0.193

Gnomad AMI AF: 0.427

Gnomad AMR AF: 0.354

Gnomad ASJ AF: 0.256

Gnomad EAS AF: 0.394

Gnomad SAS AF: 0.257

Gnomad FIN AF: 0.197

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.290

Gnomad OTH AF: 0.286

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

GnomAD4 genome AF: 0.266 AC: 40421 AN: 152064 Hom.: 5710 Cov.: 32 AF XY: 0.262 AC XY: 19509 AN XY: 74340

Gnomad4 AFR AF: 0.193

Gnomad4 AMR AF: 0.355

Gnomad4 ASJ AF: 0.256

Gnomad4 EAS AF: 0.394

Gnomad4 SAS AF: 0.256

Gnomad4 FIN AF: 0.197

Gnomad4 NFE AF: 0.290

Gnomad4 OTH AF: 0.282

Alfa AF: 0.285 Hom.: 4296

Bravo AF: 0.282

Asia WGS AF: 0.287 AC: 998 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.7
DANN	Benign	0.42

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: rs163281; hg19: chr5-16516778;