rs372004247

Variant names:

• chr6-112349900-G-A
• rs372004247
• NM_001013734.3:c.192G>A

Your query was ambiguous. Multiple possible variants found:

• chr6-112349900-G-A
• chr6-112349900-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001013734.3(RFPL4B):​c.192G>A​(p.Trp64*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,844 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: RFPL4B NM_001013734.3 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.417

Genes affected

RFPL4B (HGNC:33264): (ret finger protein like 4B) Predicted to enable metal ion binding activity. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000281613 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RFPL4B	NM_001013734.3	c.192G>A	p.Trp64*	stop_gained	Exon 3 of 3	ENST00000441065.3	NP_001013756.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RFPL4B	ENST00000441065.3	c.192G>A	p.Trp64*	stop_gained	Exon 3 of 3	2	NM_001013734.3	ENSP00000423391.1
ENSG00000281613	ENST00000587816.2	c.192G>A	p.Trp64*	stop_gained	Exon 5 of 5	5		ENSP00000487146.1
ENSG00000281613	ENST00000585611.5	c.192G>A	p.Trp64*	stop_gained	Exon 5 of 5	5		ENSP00000486440.1
ENSG00000281613	ENST00000590673.5	c.*86G>A		downstream_gene_variant		5		ENSP00000486934.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461844 Hom.: 0 Cov.: 32 AF XY: 0.00000275 AC XY: 2 AN XY: 727214

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.20	D
BayesDel_noAF	Uncertain	0.050
CADD	Pathogenic	33
DANN	Uncertain	0.99
Eigen	Benign	0.15
Eigen_PC	Benign	-0.24
FATHMM_MKL	Benign	0.037	N
Vest4		0.021
GERP RS		1.9

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: rs372004247; hg19: chr6-112671102;