NM_001145014.2:c.43C>G

Variant names:

• chr19-55761843-C-G
• rs202117713
• NM_001145014.2:c.43C>G

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001145014.2(RFPL4A):​c.43C>G​(p.Leu15Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00144 in 1,481,212 control chromosomes in the GnomAD database, including 125 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0011 (8 hom., cov: 26)
  • Exomes 𝑓: 0.0015 (117 hom.)
• Consequence: RFPL4A NM_001145014.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.877
• Publications: 1 publications found

Genes affected

RFPL4A (HGNC:16449): (ret finger protein like 4A) Predicted to enable ubiquitin-protein transferase activity. Predicted to be involved in positive regulation of transcription, DNA-templated. Predicted to be located in nucleus. Predicted to be active in chromatin and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.013174981).
• BS2: High Homozygotes in GnomAd4 at 8 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001145014.2. 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
	RFPL4A	NM_001145014.2	MANE Select	c.43C>G	p.Leu15Val	missense	Exon 2 of 3	NP_001138486.1	A6NLU0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RFPL4A	ENST00000434937.3	TSL:5 MANE Select	c.43C>G	p.Leu15Val	missense	Exon 2 of 3	ENSP00000392936.2	A6NLU0
	RFPL4A	ENST00000897443.1		c.43C>G	p.Leu15Val	missense	Exon 1 of 2	ENSP00000567502.1

Frequencies

GnomAD3 genomes AF: 0.00108 AC: 151 AN: 140326 Hom.: 8 Cov.: 26

Gnomad AFR AF: 0.000413

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00174

Gnomad ASJ AF: 0.000297

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00173

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000940 AC: 138 AN: 146758 AF XY: 0.000834

Gnomad AFR exome AF: 0.000146

Gnomad AMR exome AF: 0.000876

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000243

Gnomad NFE exome AF: 0.00177

Gnomad OTH exome AF: 0.000483

GnomAD4 exome AF: 0.00148 AC: 1987 AN: 1340770 Hom.: 117 Cov.: 36 AF XY: 0.00148 AC XY: 979 AN XY: 662416

African (AFR) AF: 0.000137 AC: 4 AN: 29266

American (AMR) AF: 0.000916 AC: 32 AN: 34946

Ashkenazi Jewish (ASJ) AF: 0.0000407 AC: 1 AN: 24588

East Asian (EAS) AF: 0.00 AC: 0 AN: 35578

South Asian (SAS) AF: 0.000388 AC: 30 AN: 77280

European-Finnish (FIN) AF: 0.000350 AC: 17 AN: 48584

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5516

European-Non Finnish (NFE) AF: 0.00180 AC: 1852 AN: 1029042

Other (OTH) AF: 0.000911 AC: 51 AN: 55970

GnomAD4 genome AF: 0.00108 AC: 151 AN: 140442 Hom.: 8 Cov.: 26 AF XY: 0.00115 AC XY: 79 AN XY: 68704

African (AFR) AF: 0.000412 AC: 15 AN: 36390

American (AMR) AF: 0.00174 AC: 25 AN: 14398

Ashkenazi Jewish (ASJ) AF: 0.000297 AC: 1 AN: 3368

East Asian (EAS) AF: 0.00 AC: 0 AN: 5082

South Asian (SAS) AF: 0.00 AC: 0 AN: 4470

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10062

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 282

European-Non Finnish (NFE) AF: 0.00173 AC: 110 AN: 63568

Other (OTH) AF: 0.00 AC: 0 AN: 1946

Alfa AF: 0.000473 Hom.: 1

ExAC AF: 0.000700 AC: 18

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.66	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	0.37
DANN	Benign	0.78
DEOGEN2	Benign	0.093	T
Eigen	Benign	-0.79
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.010	N
LIST_S2	Benign	0.39	T
M_CAP	Benign	0.0018	T
MetaRNN	Benign	0.013	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Pathogenic	3.0	M
PhyloP100		-0.88
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.076
Sift	Benign	0.36	T
Sift4G	Benign	0.14	T
Polyphen		0.81	P
Vest4		0.086
MVP		0.23
MPC		1.0
ClinPred		0.031	T
GERP RS		-2.6
Varity_R		0.028
gMVP		0.14
Mutation Taster		=100/0	polymorphism

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: rs202117713; hg19: chr19-56273209;