NM_005669.5:c.352-4919T>C

Variant names:

• chr5-112892102-A-G
• rs712665
• NM_005669.5:c.352-4919T>C

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.63
• Publications: 12 publications found

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]

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]

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.042).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.622 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005669.5. 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
	REEP5	NM_005669.5	MANE Select	c.352-4919T>C		intron	N/A	NP_005660.4
	SRP19	NM_001204199.2		c.*495A>G		3_prime_UTR	Exon 5 of 5	NP_001191128.1	A0A2U3TZN1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	REEP5	ENST00000379638.9	TSL:1 MANE Select	c.352-4919T>C		intron	N/A	ENSP00000368959.4	Q00765-1
	REEP5	ENST00000497856.6	TSL:1	n.859+348T>C		intron	N/A
	SRP19	ENST00000391338.3	TSL:6	c.*495A>G		3_prime_UTR	Exon 5 of 5	ENSP00000375133.2	A0A2U3TZN1

Frequencies

GnomAD3 genomes AF: 0.416 AC: 63224 AN: 151850 Hom.: 14510 Cov.: 31

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

GnomAD2 exomes AF: 0.331 AC: 83271 AN: 251450 AF XY: 0.327

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 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.: 34 AF XY: 0.339 AC XY: 246669 AN XY: 726922

African (AFR) AF: 0.633 AC: 21181 AN: 33444

American (AMR) AF: 0.269 AC: 12045 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.396 AC: 10344 AN: 26126

East Asian (EAS) AF: 0.156 AC: 6182 AN: 39692

South Asian (SAS) AF: 0.266 AC: 22902 AN: 86236

European-Finnish (FIN) AF: 0.343 AC: 18318 AN: 53420

Middle Eastern (MID) AF: 0.366 AC: 2109 AN: 5768

European-Non Finnish (NFE) AF: 0.347 AC: 385275 AN: 1111312

Other (OTH) AF: 0.348 AC: 20993 AN: 60364

GnomAD4 genome AF: 0.417 AC: 63320 AN: 151968 Hom.: 14542 Cov.: 31 AF XY: 0.411 AC XY: 30552 AN XY: 74300

African (AFR) AF: 0.628 AC: 25989 AN: 41386

American (AMR) AF: 0.333 AC: 5082 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.407 AC: 1412 AN: 3470

East Asian (EAS) AF: 0.180 AC: 930 AN: 5166

South Asian (SAS) AF: 0.247 AC: 1190 AN: 4820

European-Finnish (FIN) AF: 0.371 AC: 3912 AN: 10552

Middle Eastern (MID) AF: 0.364 AC: 107 AN: 294

European-Non Finnish (NFE) AF: 0.347 AC: 23581 AN: 67980

Other (OTH) AF: 0.389 AC: 824 AN: 2116

Alfa AF: 0.373 Hom.: 8063

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	6.4
DANN	Benign	0.86
PhyloP100		1.6
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

dbSNP: rs712665; hg19: chr5-112227799; COSMIC: COSV54839822; COSMIC: COSV54839822;