5-16474669-C-CT

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_001034850.3(RETREG1):c.*71_*72insA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.39 (10324 hom., cov: 0)
  • Exomes 𝑓: 0.35 (4498 hom.)
  • Failed GnomAD Quality Control
• Consequence: RETREG1 NM_001034850.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• 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 -16 ACMG points.

• BP6: Variant 5-16474669-C-CT is Benign according to our data. Variant chr5-16474669-C-CT is described in ClinVar as [Benign]. Clinvar id is 352683.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.467 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RETREG1	NM_001034850.3	c.*71_*72insA		3_prime_UTR_variant	9/9	ENST00000306320.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RETREG1	ENST00000306320.10	c.*71_*72insA		3_prime_UTR_variant	9/9	1	NM_001034850.3

Frequencies

GnomAD3 genomes AF: 0.389 AC: 51288 AN: 131846 Hom.: 10328 Cov.: 0

Gnomad AFR AF: 0.223

Gnomad AMI AF: 0.555

Gnomad AMR AF: 0.441

Gnomad ASJ AF: 0.483

Gnomad EAS AF: 0.309

Gnomad SAS AF: 0.344

Gnomad FIN AF: 0.393

Gnomad MID AF: 0.492

Gnomad NFE AF: 0.472

Gnomad OTH AF: 0.416

GnomAD4 exome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.351 AC: 391307 AN: 1113512 Hom.: 4498 Cov.: 13 AF XY: 0.349 AC XY: 194994 AN XY: 558536

Gnomad4 AFR exome AF: 0.250

Gnomad4 AMR exome AF: 0.291

Gnomad4 ASJ exome AF: 0.338

Gnomad4 EAS exome AF: 0.261

Gnomad4 SAS exome AF: 0.283

Gnomad4 FIN exome AF: 0.326

Gnomad4 NFE exome AF: 0.366

Gnomad4 OTH exome AF: 0.346

GnomAD4 genome AF: 0.389 AC: 51274 AN: 131840 Hom.: 10324 Cov.: 0 AF XY: 0.389 AC XY: 24498 AN XY: 62988

Gnomad4 AFR AF: 0.223

Gnomad4 AMR AF: 0.441

Gnomad4 ASJ AF: 0.483

Gnomad4 EAS AF: 0.309

Gnomad4 SAS AF: 0.344

Gnomad4 FIN AF: 0.393

Gnomad4 NFE AF: 0.472

Gnomad4 OTH AF: 0.413

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Hereditary sensory and autonomic neuropathy type 2 Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 10, 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;