Variant 5-16474535-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The NM_001034850.3(RETREG1):c.*206A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.319 in 617,616 control chromosomes in the GnomAD database, including 33,025 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.29 ( 7000 hom., cov: 33)

Exomes 𝑓: 0.33 ( 26025 hom. )

Consequence

RETREG1
NM_001034850.3 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 1.66

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.41).

BP6

Variant 5-16474535-T-G is Benign according to our data. Variant chr5-16474535-T-G is described in ClinVar as [Benign]. Clinvar id is 352681.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.452 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RETREG1	NM_001034850.3 linkuse as main transcript	c.*206A>C		3_prime_UTR_variant	9/9	ENST00000306320.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RETREG1	ENST00000306320.10 linkuse as main transcript	c.*206A>C		3_prime_UTR_variant	9/9	1	NM_001034850.3		Q9H6L5-1

Frequencies

GnomAD3 genomes

AF:

0.294

AC:

44630

AN:

151922

Hom.:

6983

Cov.:

show subpopulations

Gnomad AFR

AF:

0.198

Gnomad AMI

AF:

0.224

Gnomad AMR

AF:

0.353

Gnomad ASJ

AF:

0.295

Gnomad EAS

AF:

0.467

Gnomad SAS

AF:

0.395

Gnomad FIN

AF:

0.388

Gnomad MID

AF:

0.244

Gnomad NFE

AF:

0.305

Gnomad OTH

AF:

0.280

GnomAD4 exome

AF:

0.328

AC:

152582

AN:

465576

Hom.:

26025

Cov.:

AF XY:

0.330

AC XY:

81446

AN XY:

246620

show subpopulations

Gnomad4 AFR exome

AF:

0.197

Gnomad4 AMR exome

AF:

0.397

Gnomad4 ASJ exome

AF:

0.284

Gnomad4 EAS exome

AF:

0.475

Gnomad4 SAS exome

AF:

0.394

Gnomad4 FIN exome

AF:

0.363

Gnomad4 NFE exome

AF:

0.305

Gnomad4 OTH exome

AF:

0.316

GnomAD4 genome

AF:

0.294

AC:

44687

AN:

152040

Hom.:

7000

Cov.:

AF XY:

0.298

AC XY:

22132

AN XY:

74314

show subpopulations

Gnomad4 AFR

AF:

0.198

Gnomad4 AMR

AF:

0.354

Gnomad4 ASJ

AF:

0.295

Gnomad4 EAS

AF:

0.467

Gnomad4 SAS

AF:

0.396

Gnomad4 FIN

AF:

0.388

Gnomad4 NFE

AF:

0.305

Gnomad4 OTH

AF:

0.288

Alfa

AF:

0.289

Hom.:

6540

Bravo

AF:

0.288

Asia WGS

AF:

0.432

AC:

1500

AN:

3472

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 26, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Neuropathy, hereditary sensory and autonomic, type 2B

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.41

CADD

Benign

9.9

DANN

Benign

0.85

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over