5-16474669-C-CTTTTTTTTTTTTTTTTTTTTTTTTTATTTTTTTTTTTTTTT

Variant names:

• chr5-16474669-C-CTTTTTTTTTTTTTTTTTTTTTTTTTATTTTTTTTTTTTTTT
• rs200951949
• NM_001034850.3:c.*71_*72insAAAAAAAAAAAAAAATAAAAAAAAAAAAAAAAAAAAAAAAA

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001034850.3(RETREG1):​c.*71_*72insAAAAAAAAAAAAAAATAAAAAAAAAAAAAAAAAAAAAAAAA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 0)
  • Exomes 𝑓: 0.0000026 (0 hom.)
• Consequence: RETREG1 NM_001034850.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.728
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

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.*71_*72insAAAAAAAAAAAAAAATAAAAAAAAAAAAAAAAAAAAAAAAA		3_prime_UTR	Exon 9 of 9	NP_001030022.1	Q9H6L5-1
	RETREG1	NM_019000.5		c.*71_*72insAAAAAAAAAAAAAAATAAAAAAAAAAAAAAAAAAAAAAAAA		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.*71_*72insAAAAAAAAAAAAAAATAAAAAAAAAAAAAAAAAAAAAAAAA		3_prime_UTR	Exon 9 of 9	ENSP00000304642.9	Q9H6L5-1
	RETREG1	ENST00000399793.6	TSL:1	c.*71_*72insAAAAAAAAAAAAAAATAAAAAAAAAAAAAAAAAAAAAAAAA		3_prime_UTR	Exon 7 of 7	ENSP00000382691.2	Q9H6L5-2
	RETREG1	ENST00000510362.6	TSL:1	n.*71_*72insAAAAAAAAAAAAAAATAAAAAAAAAAAAAAAAAAAAAAAAA		non_coding_transcript_exon	Exon 7 of 8	ENSP00000425089.2	H0Y9U4

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome AF: 0.00000265 AC: 3 AN: 1133270 Hom.: 0 Cov.: 13 AF XY: 0.00000352 AC XY: 2 AN XY: 568546

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 24974

American (AMR) AF: 0.00 AC: 0 AN: 26008

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20182

East Asian (EAS) AF: 0.0000291 AC: 1 AN: 34312

South Asian (SAS) AF: 0.0000314 AC: 2 AN: 63662

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 35868

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4554

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 875668

Other (OTH) AF: 0.00 AC: 0 AN: 48042

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000102688), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.73

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs200951949; hg19: chr5-16474778;