rs3317

Positions:

• chr5-112876454-G-A

Variant summary

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

The NM_005669.5(REEP5):​c.*2332C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.434 in 152,024 control chromosomes in the GnomAD database, including 16,953 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 0.43 (16953 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: REEP5 NM_005669.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.239

Genes affected

REEP5 (HGNC:30077): (receptor accessory protein 5) Predicted to be involved in endoplasmic reticulum organization and regulation of intracellular transport. Located in endoplasmic reticulum tubular network. [provided by Alliance of Genome Resources, Apr 2022]

SRP19 (HGNC:11300): (signal recognition particle 19) Enables 7S RNA binding activity. Contributes to ribosome binding activity. Predicted to be involved in SRP-dependent cotranslational protein targeting to membrane, signal sequence recognition. Located in nucleolus. Part of signal recognition particle, endoplasmic reticulum targeting. [provided by Alliance of Genome Resources, Apr 2022]

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 (EAS) allele frequency at 95% confidence interval = 0.64 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
REEP5	NM_005669.5	c.*2332C>T		3_prime_UTR_variant	5/5	ENST00000379638.9	NP_005660.4
SRP19	NM_001204199.2	c.301+11722G>A		intron_variant			NP_001191128.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
REEP5	ENST00000379638.9	c.*2332C>T		3_prime_UTR_variant	5/5	1	NM_005669.5	ENSP00000368959	P1

Frequencies

GnomAD3 genomes AF: 0.434 AC: 65952 AN: 151906 Hom.: 16955 Cov.: 32

Gnomad AFR AF: 0.142

Gnomad AMI AF: 0.571

Gnomad AMR AF: 0.556

Gnomad ASJ AF: 0.501

Gnomad EAS AF: 0.659

Gnomad SAS AF: 0.571

Gnomad FIN AF: 0.517

Gnomad MID AF: 0.487

Gnomad NFE AF: 0.538

Gnomad OTH AF: 0.470

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.434 AC: 65949 AN: 152024 Hom.: 16953 Cov.: 32 AF XY: 0.438 AC XY: 32568 AN XY: 74314

Gnomad4 AFR AF: 0.142

Gnomad4 AMR AF: 0.556

Gnomad4 ASJ AF: 0.501

Gnomad4 EAS AF: 0.658

Gnomad4 SAS AF: 0.572

Gnomad4 FIN AF: 0.517

Gnomad4 NFE AF: 0.538

Gnomad4 OTH AF: 0.469

Alfa AF: 0.529 Hom.: 43582

Bravo AF: 0.425

Asia WGS AF: 0.565 AC: 1961 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	3.8
DANN	Benign	0.58

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs3317; hg19: chr5-112212151;