chr5-16479810-G-A

Variant names:

• chr5-16479810-G-A
• rs16868670
• NM_001034850.3:c.671-823C>T

Variant summary

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

The NM_001034850.3(RETREG1):​c.671-823C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.196 in 152,004 control chromosomes in the GnomAD database, including 3,309 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 0.20 (3309 hom., cov: 32)
• Consequence: RETREG1 NM_001034850.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.273
• Publications: 2 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=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.326 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.671-823C>T		intron	N/A	NP_001030022.1
	RETREG1	NM_019000.5		c.248-823C>T		intron	N/A	NP_061873.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RETREG1	ENST00000306320.10	TSL:1 MANE Select	c.671-823C>T		intron	N/A	ENSP00000304642.9
	RETREG1	ENST00000399793.6	TSL:1	c.248-823C>T		intron	N/A	ENSP00000382691.2
	RETREG1	ENST00000510362.6	TSL:1	n.146-823C>T		intron	N/A	ENSP00000425089.2

Frequencies

GnomAD3 genomes AF: 0.197 AC: 29869 AN: 151886 Hom.: 3321 Cov.: 32

Gnomad AFR AF: 0.0849

Gnomad AMI AF: 0.231

Gnomad AMR AF: 0.227

Gnomad ASJ AF: 0.232

Gnomad EAS AF: 0.310

Gnomad SAS AF: 0.340

Gnomad FIN AF: 0.210

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.234

Gnomad OTH AF: 0.211

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

GnomAD4 genome AF: 0.196 AC: 29859 AN: 152004 Hom.: 3309 Cov.: 32 AF XY: 0.198 AC XY: 14732 AN XY: 74292

African (AFR) AF: 0.0848 AC: 3517 AN: 41492

American (AMR) AF: 0.227 AC: 3463 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.232 AC: 805 AN: 3466

East Asian (EAS) AF: 0.309 AC: 1594 AN: 5158

South Asian (SAS) AF: 0.340 AC: 1638 AN: 4820

European-Finnish (FIN) AF: 0.210 AC: 2220 AN: 10566

Middle Eastern (MID) AF: 0.241 AC: 71 AN: 294

European-Non Finnish (NFE) AF: 0.234 AC: 15903 AN: 67944

Other (OTH) AF: 0.208 AC: 439 AN: 2106

Alfa AF: 0.218 Hom.: 1685

Bravo AF: 0.191

Asia WGS AF: 0.264 AC: 918 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.7
DANN	Benign	0.51
PhyloP100		-0.27
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: rs16868670; hg19: chr5-16479919;