rs6604026

chr1-92838046-T-Cchr1-92838046-T-G

Variant summary

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

The NM_000969.5(RPL5):c.705+413T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.257 in 152,136 control chromosomes in the GnomAD database, including 5,327 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 0.26 (5327 hom., cov: 33)
• Consequence: RPL5 NM_000969.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.491

Genes affected

RPL5 (HGNC:10360): (ribosomal protein L5) Ribosomes, the organelles that catalyze protein synthesis, consist of a small 40S subunit and a large 60S subunit. Together these subunits are composed of four RNA species and approximately 80 structurally distinct proteins. This gene encodes a member of the L18P family of ribosomal proteins and component of the 60S subunit. The encoded protein binds 5S rRNA to form a stable complex called the 5S ribonucleoprotein particle (RNP), which is necessary for the transport of nonribosome-associated cytoplasmic 5S rRNA to the nucleolus for assembly into ribosomes. The encoded protein may also function to inhibit tumorigenesis through the activation of downstream tumor suppressors and the downregulation of oncoprotein expression. Mutations in this gene have been identified in patients with Diamond-Blackfan Anemia (DBA). This gene is co-transcribed with the small nucleolar RNA gene U21, which is located in its fifth intron. As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed throughout the genome. [provided by RefSeq, Mar 2017]

DIPK1A (HGNC:32213): (divergent protein kinase domain 1A) This gene encodes a member of the FAM69 family of cysteine-rich type II transmembrane proteins. These proteins localize to the endoplasmic reticulum but their specific functions are unknown. 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=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.269 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RPL5	NM_000969.5	c.705+413T>C		intron_variant		ENST00000370321.8
DIPK1A	NM_001252273.2	c.475-5012A>G		intron_variant
RPL5	NR_146333.1	n.764+413T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RPL5	ENST00000370321.8	c.705+413T>C		intron_variant		1	NM_000969.5	P1

Frequencies

GnomAD3 genomes AF: 0.257 AC: 39008 AN: 152016 Hom.: 5322 Cov.: 33

Gnomad AFR AF: 0.272

Gnomad AMI AF: 0.254

Gnomad AMR AF: 0.262

Gnomad ASJ AF: 0.222

Gnomad EAS AF: 0.0148

Gnomad SAS AF: 0.143

Gnomad FIN AF: 0.268

Gnomad MID AF: 0.310

Gnomad NFE AF: 0.272

Gnomad OTH AF: 0.280

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

GnomAD4 genome AF: 0.257 AC: 39030 AN: 152136 Hom.: 5327 Cov.: 33 AF XY: 0.253 AC XY: 18815 AN XY: 74380

Gnomad4 AFR AF: 0.271

Gnomad4 AMR AF: 0.262

Gnomad4 ASJ AF: 0.222

Gnomad4 EAS AF: 0.0150

Gnomad4 SAS AF: 0.142

Gnomad4 FIN AF: 0.268

Gnomad4 NFE AF: 0.272

Gnomad4 OTH AF: 0.276

Alfa AF: 0.257 Hom.: 11342

Bravo AF: 0.257

Asia WGS AF: 0.104 AC: 364 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	6.5
Dann	Benign	0.63
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs6604026; hg19: chr1-93303603;