15-66503642-A-C

Variant names:

• chr15-66503642-A-C
• rs8043062
• NM_000968.4:c.4-113T>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_000968.4(RPL4):​c.4-113T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: RPL4 NM_000968.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.213
• Publications: 7 publications found

Genes affected

RPL4 (HGNC:10353): (ribosomal protein L4) Ribosomes, the organelles that catalyze protein synthesis, consist of a small 40S subunit and a large 60S subunit. Together these subunits are composed of 4 RNA species and approximately 80 structurally distinct proteins. This gene encodes a ribosomal protein that is a component of the 60S subunit. The protein belongs to the L4E family of ribosomal proteins. It is located in the cytoplasm. As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed through the genome. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000968.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPL4	NM_000968.4	MANE Select	c.4-113T>G		intron	N/A	NP_000959.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPL4	ENST00000307961.11	TSL:1 MANE Select	c.4-113T>G		intron	N/A	ENSP00000311430.6
	RPL4	ENST00000568588.5	TSL:2	c.-279-113T>G		intron	N/A	ENSP00000454281.1
	RPL4	ENST00000569696.5	TSL:5	c.4-113T>G		intron	N/A	ENSP00000457442.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1020854 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 500416

African (AFR) AF: 0.00 AC: 0 AN: 22950

American (AMR) AF: 0.00 AC: 0 AN: 17186

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16778

East Asian (EAS) AF: 0.00 AC: 0 AN: 32740

South Asian (SAS) AF: 0.00 AC: 0 AN: 50534

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 43980

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4646

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 788120

Other (OTH) AF: 0.00 AC: 0 AN: 43920

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.5
DANN	Benign	0.36
PhyloP100		0.21
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

Other links and lift over

dbSNP: rs8043062; hg19: chr15-66795980;