5-16474669-CT-C

Position:

• chr5-16474669-CT-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001034850.3(RETREG1):​c.*71del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0054 (6 hom., cov: 0)
  • Exomes 𝑓: 0.081 (1 hom.)
• Consequence: RETREG1 NM_001034850.3 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.728

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 -10 ACMG points.

• BP6: Variant 5-16474669-CT-C is Benign according to our data. Variant chr5-16474669-CT-C is described in ClinVar as [Likely_benign]. Clinvar id is 1199642.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAdExome4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.147 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RETREG1	NM_001034850.3	c.*71del		3_prime_UTR_variant	9/9	ENST00000306320.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RETREG1	ENST00000306320.10	c.*71del		3_prime_UTR_variant	9/9	1	NM_001034850.3

Frequencies

GnomAD3 genomes AF: 0.00540 AC: 712 AN: 131964 Hom.: 6 Cov.: 0

Gnomad AFR AF: 0.00998

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00297

Gnomad ASJ AF: 0.00981

Gnomad EAS AF: 0.0270

Gnomad SAS AF: 0.00729

Gnomad FIN AF: 0.00129

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00193

Gnomad OTH AF: 0.00513

GnomAD4 exome AF: 0.0808 AC: 88396 AN: 1094518 Hom.: 1 Cov.: 13 AF XY: 0.0814 AC XY: 44622 AN XY: 548194

Gnomad4 AFR exome AF: 0.135

Gnomad4 AMR exome AF: 0.0978

Gnomad4 ASJ exome AF: 0.0908

Gnomad4 EAS exome AF: 0.150

Gnomad4 SAS exome AF: 0.105

Gnomad4 FIN exome AF: 0.0836

Gnomad4 NFE exome AF: 0.0740

Gnomad4 OTH exome AF: 0.0843

GnomAD4 genome AF: 0.00541 AC: 714 AN: 131958 Hom.: 6 Cov.: 0 AF XY: 0.00547 AC XY: 345 AN XY: 63032

Gnomad4 AFR AF: 0.0100

Gnomad4 AMR AF: 0.00289

Gnomad4 ASJ AF: 0.00981

Gnomad4 EAS AF: 0.0271

Gnomad4 SAS AF: 0.00733

Gnomad4 FIN AF: 0.00129

Gnomad4 NFE AF: 0.00193

Gnomad4 OTH AF: 0.00569

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 21, 2019

- -

Computational scores

Source: dbNSFP v4.3

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: rs200951949; hg19: chr5-16474778;