Genetic Variant NM_005669.5:c.352-4919T>C (chr5-112892102-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_005669.5(REEP5):c.352-4919T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.349 in 1,613,054 control chromosomes in the GnomAD database, including 103,085 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 0.42 ( 14542 hom., cov: 31)

Exomes 𝑓: 0.34 ( 88543 hom. )

Consequence

REEP5
NM_005669.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.63

Variant links:

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]

REEP5 links:

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]

SRP19 links:

ZRSR2P1 (HGNC:12456): (ZRSR2 pseudogene 1) Predicted to enable pre-mRNA 3'-splice site binding activity. Predicted to be involved in mRNA splicing, via spliceosome. Predicted to be part of U2AF complex and spliceosomal complex. [provided by Alliance of Genome Resources, Apr 2022]

ZRSR2P1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.66).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.622 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
REEP5	NM_005669.5 link	c.352-4919T>C	intron_variant	Intron 3 of 4	ENST00000379638.9	NP_005660.4	Q00765-1
SRP19	NM_001204199.2 link	c.*495A>G	3_prime_UTR_variant	Exon 5 of 5		NP_001191128.1	A0A2U3TZN1
ZRSR2P1		n.112892102A>G	intragenic_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
REEP5	ENST00000379638.9 link	c.352-4919T>C		intron_variant	Intron 3 of 4	1	NM_005669.5	ENSP00000368959.4		Q00765-1

Frequencies

GnomAD3 genomes

AF:

0.416

AC:

63224

AN:

151850

Hom.:

14510

Cov.:

show subpopulations

Gnomad AFR

AF:

0.628

Gnomad AMI

AF:

0.322

Gnomad AMR

AF:

0.333

Gnomad ASJ

AF:

0.407

Gnomad EAS

AF:

0.180

Gnomad SAS

AF:

0.247

Gnomad FIN

AF:

0.371

Gnomad MID

AF:

0.370

Gnomad NFE

AF:

0.347

Gnomad OTH

AF:

0.386

GnomAD3 exomes

AF:

0.331

AC:

83271

AN:

251450

Hom.:

15231

AF XY:

0.327

AC XY:

44502

AN XY:

135896

show subpopulations

Gnomad AFR exome

AF:

0.638

Gnomad AMR exome

AF:

0.261

Gnomad ASJ exome

AF:

0.395

Gnomad EAS exome

AF:

0.174

Gnomad SAS exome

AF:

0.263

Gnomad FIN exome

AF:

0.355

Gnomad NFE exome

AF:

0.342

Gnomad OTH exome

AF:

0.330

GnomAD4 exome

AF:

0.342

AC:

499349

AN:

1461086

Hom.:

88543

Cov.:

AF XY:

0.339

AC XY:

246669

AN XY:

726922

show subpopulations

Gnomad4 AFR exome

AF:

0.633

Gnomad4 AMR exome

AF:

0.269

Gnomad4 ASJ exome

AF:

0.396

Gnomad4 EAS exome

AF:

0.156

Gnomad4 SAS exome

AF:

0.266

Gnomad4 FIN exome

AF:

0.343

Gnomad4 NFE exome

AF:

0.347

Gnomad4 OTH exome

AF:

0.348

GnomAD4 genome

AF:

0.417

AC:

63320

AN:

151968

Hom.:

14542

Cov.:

AF XY:

0.411

AC XY:

30552

AN XY:

74300

show subpopulations

Gnomad4 AFR

AF:

0.628

Gnomad4 AMR

AF:

0.333

Gnomad4 ASJ

AF:

0.407

Gnomad4 EAS

AF:

0.180

Gnomad4 SAS

AF:

0.247

Gnomad4 FIN

AF:

0.371

Gnomad4 NFE

AF:

0.347

Gnomad4 OTH

AF:

0.389

Alfa

AF:

0.329

Hom.:

4687

Bravo

AF:

0.422

Asia WGS

AF:

0.248

AC:

868

AN:

3478

EpiCase

AF:

0.352

EpiControl

AF:

0.354

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.66

CADD

Benign

6.4

DANN

Benign

0.86

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over