5-16557758-C-T

Variant names:

• chr5-16557758-C-T
• rs10041159
• NM_001034850.3:c.458+8005G>A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001034850.3(RETREG1):​c.458+8005G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.375 in 151,972 control chromosomes in the GnomAD database, including 10,807 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.38 (10807 hom., cov: 33)
• Consequence: RETREG1 NM_001034850.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0470

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.454 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RETREG1	NM_001034850.3	c.458+8005G>A		intron_variant	Intron 3 of 8	ENST00000306320.10	NP_001030022.1
RETREG1	XM_011514053.4	c.458+8005G>A		intron_variant	Intron 3 of 9		XP_011512355.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RETREG1	ENST00000306320.10	c.458+8005G>A		intron_variant	Intron 3 of 8	1	NM_001034850.3	ENSP00000304642.9

Frequencies

GnomAD3 genomes AF: 0.375 AC: 56935 AN: 151854 Hom.: 10793 Cov.: 33

Gnomad AFR AF: 0.340

Gnomad AMI AF: 0.384

Gnomad AMR AF: 0.332

Gnomad ASJ AF: 0.404

Gnomad EAS AF: 0.401

Gnomad SAS AF: 0.469

Gnomad FIN AF: 0.386

Gnomad MID AF: 0.376

Gnomad NFE AF: 0.395

Gnomad OTH AF: 0.340

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.375 AC: 56995 AN: 151972 Hom.: 10807 Cov.: 33 AF XY: 0.373 AC XY: 27719 AN XY: 74286

Gnomad4 AFR AF: 0.340

Gnomad4 AMR AF: 0.332

Gnomad4 ASJ AF: 0.404

Gnomad4 EAS AF: 0.400

Gnomad4 SAS AF: 0.471

Gnomad4 FIN AF: 0.386

Gnomad4 NFE AF: 0.395

Gnomad4 OTH AF: 0.345

Alfa AF: 0.288 Hom.: 1033

Bravo AF: 0.366

Asia WGS AF: 0.445 AC: 1547 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	5.5
DANN	Benign	0.80

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

Other links and lift over

dbSNP: rs10041159; hg19: chr5-16557867;