5-16588931-T-C

Variant names:

• chr5-16588931-T-C
• rs2451852
• NM_001034850.3:c.321-16829A>G

Variant summary

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

The NM_001034850.3(RETREG1):​c.321-16829A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.135 in 152,202 control chromosomes in the GnomAD database, including 1,398 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 0.13 (1398 hom., cov: 33)
• Consequence: RETREG1 NM_001034850.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.789
• 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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.156 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001034850.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RETREG1	NM_001034850.3	MANE Select	c.321-16829A>G		intron	N/A	NP_001030022.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RETREG1	ENST00000306320.10	TSL:1 MANE Select	c.321-16829A>G		intron	N/A	ENSP00000304642.9
	RETREG1	ENST00000682229.1		c.321-16829A>G		intron	N/A	ENSP00000507342.1
	RETREG1	ENST00000682564.1		c.321-16829A>G		intron	N/A	ENSP00000508099.1

Frequencies

GnomAD3 genomes AF: 0.135 AC: 20490 AN: 152088 Hom.: 1392 Cov.: 33

Gnomad AFR AF: 0.128

Gnomad AMI AF: 0.125

Gnomad AMR AF: 0.0779

Gnomad ASJ AF: 0.149

Gnomad EAS AF: 0.0406

Gnomad SAS AF: 0.121

Gnomad FIN AF: 0.146

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.158

Gnomad OTH AF: 0.115

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

GnomAD4 genome AF: 0.135 AC: 20524 AN: 152202 Hom.: 1398 Cov.: 33 AF XY: 0.131 AC XY: 9765 AN XY: 74416

African (AFR) AF: 0.129 AC: 5351 AN: 41526

American (AMR) AF: 0.0776 AC: 1186 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.149 AC: 518 AN: 3468

East Asian (EAS) AF: 0.0403 AC: 209 AN: 5182

South Asian (SAS) AF: 0.121 AC: 586 AN: 4828

European-Finnish (FIN) AF: 0.146 AC: 1547 AN: 10598

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

European-Non Finnish (NFE) AF: 0.158 AC: 10744 AN: 67994

Other (OTH) AF: 0.113 AC: 239 AN: 2112

Alfa AF: 0.134 Hom.: 813

Bravo AF: 0.128

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	5.1
DANN	Benign	0.72
PhyloP100		-0.79
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: rs2451852; hg19: chr5-16589040;