5-16474669-CTTTTTTT-CTTTTTTTT

Variant names:

• chr5-16474669-C-CT
• rs200951949
• NM_001034850.3:c.*71dupA

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_001034850.3(RETREG1):​c.*71dupA 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
• Publications: 2 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 -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 VariationId 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.

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.*71dupA		3_prime_UTR	Exon 9 of 9	NP_001030022.1	Q9H6L5-1
	RETREG1	NM_019000.5		c.*71dupA		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.*71dupA		3_prime_UTR	Exon 9 of 9	ENSP00000304642.9	Q9H6L5-1
	RETREG1	ENST00000399793.6	TSL:1	c.*71dupA		3_prime_UTR	Exon 7 of 7	ENSP00000382691.2	Q9H6L5-2
	RETREG1	ENST00000510362.6	TSL:1	n.*71dupA		non_coding_transcript_exon	Exon 7 of 8	ENSP00000425089.2	H0Y9U4

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

African (AFR) AF: 0.250 AC: 6060 AN: 24280

American (AMR) AF: 0.291 AC: 7456 AN: 25584

Ashkenazi Jewish (ASJ) AF: 0.338 AC: 6703 AN: 19828

East Asian (EAS) AF: 0.261 AC: 8673 AN: 33282

South Asian (SAS) AF: 0.283 AC: 17670 AN: 62394

European-Finnish (FIN) AF: 0.326 AC: 11471 AN: 35134

Middle Eastern (MID) AF: 0.369 AC: 1661 AN: 4500

European-Non Finnish (NFE) AF: 0.366 AC: 315346 AN: 861442

Other (OTH) AF: 0.346 AC: 16267 AN: 47068

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

African (AFR) AF: 0.223 AC: 7872 AN: 35290

American (AMR) AF: 0.441 AC: 5793 AN: 13144

Ashkenazi Jewish (ASJ) AF: 0.483 AC: 1573 AN: 3258

East Asian (EAS) AF: 0.309 AC: 1382 AN: 4466

South Asian (SAS) AF: 0.344 AC: 1405 AN: 4086

European-Finnish (FIN) AF: 0.393 AC: 2432 AN: 6192

Middle Eastern (MID) AF: 0.475 AC: 116 AN: 244

European-Non Finnish (NFE) AF: 0.472 AC: 29493 AN: 62536

Other (OTH) AF: 0.413 AC: 725 AN: 1754

Alfa AF: 0.171 Hom.: 377

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Hereditary sensory and autonomic neuropathy type 2 (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.73
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs200951949; hg19: chr5-16474778;