5-16474285-G-GA

Variant summary

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

The NM_001034850.3(RETREG1):c.*455_*456insT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0775 in 154,714 control chromosomes in the GnomAD database, including 1,157 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.079 (1156 hom., cov: 32)
  • Exomes 𝑓: 0.012 (1 hom.)
• Consequence: RETREG1 NM_001034850.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.337

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 5-16474285-G-GA is Benign according to our data. Variant chr5-16474285-G-GA is described in ClinVar as [Benign]. Clinvar id is 352680.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.231 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RETREG1	NM_001034850.3	c.*455_*456insT		3_prime_UTR_variant	9/9	ENST00000306320.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RETREG1	ENST00000306320.10	c.*455_*456insT		3_prime_UTR_variant	9/9	1	NM_001034850.3

Frequencies

GnomAD3 genomes AF: 0.0789 AC: 11897 AN: 150810 Hom.: 1147 Cov.: 32

Gnomad AFR AF: 0.235

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0367

Gnomad ASJ AF: 0.00867

Gnomad EAS AF: 0.00466

Gnomad SAS AF: 0.00438

Gnomad FIN AF: 0.00560

Gnomad MID AF: 0.0290

Gnomad NFE AF: 0.0212

Gnomad OTH AF: 0.0629

GnomAD4 exome AF: 0.0118 AC: 45 AN: 3798 Hom.: 1 Cov.: 0 AF XY: 0.0133 AC XY: 27 AN XY: 2032

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0137

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0116

Gnomad4 SAS exome AF: 0.00461

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0131

Gnomad4 OTH exome AF: 0.0119

GnomAD4 genome AF: 0.0792 AC: 11948 AN: 150916 Hom.: 1156 Cov.: 32 AF XY: 0.0766 AC XY: 5640 AN XY: 73622

Gnomad4 AFR AF: 0.235

Gnomad4 AMR AF: 0.0366

Gnomad4 ASJ AF: 0.00867

Gnomad4 EAS AF: 0.00467

Gnomad4 SAS AF: 0.00438

Gnomad4 FIN AF: 0.00560

Gnomad4 NFE AF: 0.0212

Gnomad4 OTH AF: 0.0623

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

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

- -

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: rs140982908; hg19: chr5-16474394;