rs32147

Variant names:

• chr5-16474535-T-G
• rs32147
• NM_001034850.3:c.*206A>C

Your query was ambiguous. Multiple possible variants found:

• chr5-16474535-T-G
• chr5-16474535-T-C

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 1.66
• Publications: 8 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 -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 VariationId 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.

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.*206A>C		3_prime_UTR	Exon 9 of 9	NP_001030022.1	Q9H6L5-1
	RETREG1	NM_019000.5		c.*206A>C		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.*206A>C		3_prime_UTR	Exon 9 of 9	ENSP00000304642.9	Q9H6L5-1
	RETREG1	ENST00000399793.6	TSL:1	c.*206A>C		3_prime_UTR	Exon 7 of 7	ENSP00000382691.2	Q9H6L5-2
	RETREG1	ENST00000510362.6	TSL:1	n.*92+114A>C		intron	N/A	ENSP00000425089.2	H0Y9U4

Frequencies

GnomAD3 genomes AF: 0.294 AC: 44630 AN: 151922 Hom.: 6983 Cov.: 33

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.: 6 AF XY: 0.330 AC XY: 81446 AN XY: 246620

African (AFR) AF: 0.197 AC: 2467 AN: 12552

American (AMR) AF: 0.397 AC: 6836 AN: 17210

Ashkenazi Jewish (ASJ) AF: 0.284 AC: 3748 AN: 13198

East Asian (EAS) AF: 0.475 AC: 13920 AN: 29276

South Asian (SAS) AF: 0.394 AC: 17303 AN: 43902

European-Finnish (FIN) AF: 0.363 AC: 9684 AN: 26668

Middle Eastern (MID) AF: 0.256 AC: 488 AN: 1908

European-Non Finnish (NFE) AF: 0.305 AC: 89950 AN: 294948

Other (OTH) AF: 0.316 AC: 8186 AN: 25914

GnomAD4 genome AF: 0.294 AC: 44687 AN: 152040 Hom.: 7000 Cov.: 33 AF XY: 0.298 AC XY: 22132 AN XY: 74314

African (AFR) AF: 0.198 AC: 8238 AN: 41514

American (AMR) AF: 0.354 AC: 5396 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.295 AC: 1025 AN: 3470

East Asian (EAS) AF: 0.467 AC: 2410 AN: 5160

South Asian (SAS) AF: 0.396 AC: 1909 AN: 4818

European-Finnish (FIN) AF: 0.388 AC: 4087 AN: 10542

Middle Eastern (MID) AF: 0.259 AC: 75 AN: 290

European-Non Finnish (NFE) AF: 0.305 AC: 20734 AN: 67958

Other (OTH) AF: 0.288 AC: 609 AN: 2112

Alfa AF: 0.289 Hom.: 8460

Bravo AF: 0.288

Asia WGS AF: 0.432 AC: 1500 AN: 3472

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Neuropathy, hereditary sensory and autonomic, type 2B (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
CADD	Benign	9.9
DANN	Benign	0.85
PhyloP100		1.7
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

Other links and lift over

dbSNP: rs32147; hg19: chr5-16474644;