Genetic Variant RETREG1:c.*56_*71dupAAAAAAAAAAAAAAAA (chr5-16474669-C-CTTTTTTTTTTTTTTTT) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_001034850.3(RETREG1):c.*56_*71dupAAAAAAAAAAAAAAAA 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: 𝑓 0.0 ( 0 hom., cov: 0)

Exomes 𝑓: 0.0000018 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

RETREG1
NM_001034850.3 3_prime_UTR

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.728

Publications

0 publications found

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 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

RETREG1 links:

ENSG00000289112 (HGNC:):

ENSG00000289112 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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.56_71dupAAAAAAAAAAAAAAAA		3_prime_UTR	Exon 9 of 9	NP_001030022.1	Q9H6L5-1
	RETREG1	NM_019000.5		c.56_71dupAAAAAAAAAAAAAAAA		3_prime_UTR	Exon 7 of 7	NP_061873.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
RETREG1	ENST00000306320.10	TSL:1 MANE Select	c.56_71dupAAAAAAAAAAAAAAAA	3_prime_UTR	Exon 9 of 9	ENSP00000304642.9	Q9H6L5-1
RETREG1	ENST00000399793.6	TSL:1	c.56_71dupAAAAAAAAAAAAAAAA	3_prime_UTR	Exon 7 of 7	ENSP00000382691.2	Q9H6L5-2
RETREG1	ENST00000510362.6	TSL:1	n.56_71dupAAAAAAAAAAAAAAAA	non_coding_transcript_exon	Exon 7 of 8	ENSP00000425089.2	H0Y9U4

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

131996

Hom.:

Cov.:

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000176

AC:

AN:

1133256

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

568540

show subpopulations

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

African (AFR)

AF:

0.00

AC:

AN:

24974

American (AMR)

AF:

0.00

AC:

AN:

26008

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

20182

East Asian (EAS)

AF:

0.0000291

AC:

AN:

34308

South Asian (SAS)

AF:

0.00

AC:

AN:

63658

European-Finnish (FIN)

AF:

0.00

AC:

AN:

35868

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4554

European-Non Finnish (NFE)

AF:

0.00000114

AC:

AN:

875664

Other (OTH)

AF:

0.00

AC:

AN:

48040

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.00233887), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.350

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

131996

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

63040

African (AFR)

AF:

0.00

AC:

AN:

35280

American (AMR)

AF:

0.00

AC:

AN:

13154

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3264

East Asian (EAS)

AF:

0.00

AC:

AN:

4484

South Asian (SAS)

AF:

0.00

AC:

AN:

4118

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6196

Middle Eastern (MID)

AF:

0.00

AC:

AN:

264

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

62612

Other (OTH)

AF:

0.00

AC:

AN:

1754

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

Publications

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5-16474669-CTTTTTTT-CTTTTTTTTTTTTTTTTTTTTTTT

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over