rs26016

Variant names:

• chr5-16473729-C-T
• rs26016
• NM_001034850.3:c.*1012G>A

Your query was ambiguous. Multiple possible variants found:

• chr5-16473729-C-T
• chr5-16473729-C-A
• chr5-16473729-C-G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001034850.3(RETREG1):​c.*1012G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.373 in 152,010 control chromosomes in the GnomAD database, including 10,764 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.37 (10754 hom., cov: 33)
  • Exomes 𝑓: 0.41 (10 hom.)
• Consequence: RETREG1 NM_001034850.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0560
• Publications: 4 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):

• hereditary sensory and autonomic neuropathy

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• 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

ENSG00000289112 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 5-16473729-C-T is Benign according to our data. Variant chr5-16473729-C-T is described in ClinVar as Benign. ClinVar VariationId is 352675.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.445 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RETREG1	NM_001034850.3	MANE Select	c.*1012G>A		3_prime_UTR	Exon 9 of 9	NP_001030022.1	Q9H6L5-1
	RETREG1	NM_019000.5		c.*1012G>A		3_prime_UTR	Exon 7 of 7	NP_061873.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RETREG1	ENST00000306320.10	TSL:1 MANE Select	c.*1012G>A		3_prime_UTR	Exon 9 of 9	ENSP00000304642.9	Q9H6L5-1
	RETREG1	ENST00000399793.6	TSL:1	c.*1012G>A		3_prime_UTR	Exon 7 of 7	ENSP00000382691.2	Q9H6L5-2
	RETREG1	ENST00000510362.6	TSL:1	n.*93-383G>A		intron	N/A	ENSP00000425089.2	H0Y9U4

Frequencies

GnomAD3 genomes AF: 0.372 AC: 56486 AN: 151780 Hom.: 10720 Cov.: 33

Gnomad AFR AF: 0.435

Gnomad AMI AF: 0.224

Gnomad AMR AF: 0.389

Gnomad ASJ AF: 0.302

Gnomad EAS AF: 0.460

Gnomad SAS AF: 0.398

Gnomad FIN AF: 0.393

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.325

Gnomad OTH AF: 0.346

GnomAD4 exome AF: 0.409 AC: 45 AN: 110 Hom.: 10 Cov.: 0 AF XY: 0.397 AC XY: 31 AN XY: 78

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.407 AC: 44 AN: 108

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AF: 0.500 AC: 1 AN: 2

GnomAD4 genome AF: 0.373 AC: 56591 AN: 151900 Hom.: 10754 Cov.: 33 AF XY: 0.374 AC XY: 27747 AN XY: 74226

African (AFR) AF: 0.435 AC: 18031 AN: 41438

American (AMR) AF: 0.389 AC: 5943 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.302 AC: 1047 AN: 3464

East Asian (EAS) AF: 0.460 AC: 2373 AN: 5156

South Asian (SAS) AF: 0.399 AC: 1921 AN: 4814

European-Finnish (FIN) AF: 0.393 AC: 4136 AN: 10528

Middle Eastern (MID) AF: 0.296 AC: 87 AN: 294

European-Non Finnish (NFE) AF: 0.325 AC: 22107 AN: 67924

Other (OTH) AF: 0.353 AC: 742 AN: 2104

Alfa AF: 0.337 Hom.: 7711

Bravo AF: 0.375

Asia WGS AF: 0.451 AC: 1566 AN: 3474

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Neuropathy, hereditary sensory and autonomic, type 2B (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.3
DANN	Benign	0.54
PhyloP100		0.056
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: rs26016; hg19: chr5-16473838;