5-16474669-C-CTT

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_001034850.3(RETREG1):c.*71_*72insAA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0061 (7 hom., cov: 0)
  • Exomes 𝑓: 0.034 (8 hom.)
• Consequence: RETREG1 NM_001034850.3 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.728

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 -10 ACMG points.

• BP6: Variant 5-16474669-C-CTT is Benign according to our data. Variant chr5-16474669-C-CTT is described in ClinVar as [Likely_benign]. Clinvar id is 1187864.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00609 (804/131950) while in subpopulation AFR AF= 0.0172 (609/35312). AF 95% confidence interval is 0.0161. There are 7 homozygotes in gnomad4. There are 391 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RETREG1	NM_001034850.3	c.*71_*72insAA		3_prime_UTR_variant	9/9	ENST00000306320.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RETREG1	ENST00000306320.10	c.*71_*72insAA		3_prime_UTR_variant	9/9	1	NM_001034850.3

Frequencies

GnomAD3 genomes AF: 0.00609 AC: 803 AN: 131956 Hom.: 7 Cov.: 0

Gnomad AFR AF: 0.0172

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00525

Gnomad ASJ AF: 0.00307

Gnomad EAS AF: 0.00178

Gnomad SAS AF: 0.00121

Gnomad FIN AF: 0.000161

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00147

Gnomad OTH AF: 0.00570

GnomAD4 exome AF: 0.0343 AC: 38452 AN: 1121812 Hom.: 8 Cov.: 13 AF XY: 0.0341 AC XY: 19168 AN XY: 562788

Gnomad4 AFR exome AF: 0.0240

Gnomad4 AMR exome AF: 0.0286

Gnomad4 ASJ exome AF: 0.0359

Gnomad4 EAS exome AF: 0.0141

Gnomad4 SAS exome AF: 0.0259

Gnomad4 FIN exome AF: 0.0252

Gnomad4 NFE exome AF: 0.0366

Gnomad4 OTH exome AF: 0.0317

GnomAD4 genome AF: 0.00609 AC: 804 AN: 131950 Hom.: 7 Cov.: 0 AF XY: 0.00620 AC XY: 391 AN XY: 63034

Gnomad4 AFR AF: 0.0172

Gnomad4 AMR AF: 0.00525

Gnomad4 ASJ AF: 0.00307

Gnomad4 EAS AF: 0.00179

Gnomad4 SAS AF: 0.00122

Gnomad4 FIN AF: 0.000161

Gnomad4 NFE AF: 0.00147

Gnomad4 OTH AF: 0.00569

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 10, 2019

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Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs200951949; hg19: chr5-16474778;