rs372004247

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001013734.3(RFPL4B):​c.192G>T​(p.Trp64Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000146 in 1,614,026 control chromosomes in the GnomAD database, including 1 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 0.000053 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00016 (1 hom.)
• Consequence: RFPL4B NM_001013734.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.417
• Publications: 1 publications found

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

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

• BP4: Computational evidence support a benign effect (MetaRNN=0.09181246).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001013734.3. 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
	RFPL4B	NM_001013734.3	MANE Select	c.192G>T	p.Trp64Cys	missense	Exon 3 of 3	NP_001013756.2	Q6ZWI9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RFPL4B	ENST00000441065.3	TSL:2 MANE Select	c.192G>T	p.Trp64Cys	missense	Exon 3 of 3	ENSP00000423391.1	Q6ZWI9
	ENSG00000281613	ENST00000587816.2	TSL:5	c.192G>T	p.Trp64Cys	missense	Exon 5 of 5	ENSP00000487146.1	A0A0D9SG52
	RFPL4B	ENST00000962225.1		c.192G>T	p.Trp64Cys	missense	Exon 2 of 2	ENSP00000632284.1

Frequencies

GnomAD3 genomes AF: 0.0000526 AC: 8 AN: 152182 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000438 AC: 11 AN: 251304 AF XY: 0.0000368

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000462

Gnomad NFE exome AF: 0.0000792

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.000155 AC: 227 AN: 1461844 Hom.: 1 Cov.: 32 AF XY: 0.000150 AC XY: 109 AN XY: 727214

African (AFR) AF: 0.0000597 AC: 2 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86248

European-Finnish (FIN) AF: 0.000150 AC: 8 AN: 53416

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.000192 AC: 213 AN: 1111988

Other (OTH) AF: 0.0000662 AC: 4 AN: 60394

GnomAD4 genome AF: 0.0000526 AC: 8 AN: 152182 Hom.: 0 Cov.: 32 AF XY: 0.0000538 AC XY: 4 AN XY: 74342

African (AFR) AF: 0.0000724 AC: 3 AN: 41436

American (AMR) AF: 0.00 AC: 0 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5198

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10610

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000735 AC: 5 AN: 68030

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.000169 Hom.: 0

Bravo AF: 0.0000642

TwinsUK AF: 0.000539 AC: 2

ALSPAC AF: 0.00 AC: 0

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.0000247 AC: 3

EpiCase AF: 0.000218

EpiControl AF: 0.0000593

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	Uncertain	0.44
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	13
DANN	Benign	0.35
DEOGEN2	Benign	0.085	T
Eigen	Benign	-0.81
Eigen_PC	Benign	-0.88
FATHMM_MKL	Benign	0.087	N
LIST_S2	Benign	0.58	T
M_CAP	Benign	0.0058	T
MetaRNN	Benign	0.092	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.5	L
PhyloP100		0.42
PrimateAI	Benign	0.41	T
PROVEAN	Uncertain	-4.0	D
REVEL	Benign	0.10
Sift	Benign	0.24	T
Sift4G	Pathogenic	0.0	D
Polyphen		0.038	B
Vest4		0.31
MutPred		0.58		Loss of catalytic residue at W64 (P = 0.0442)
MVP		0.45
MPC		0.21
ClinPred		0.076	T
GERP RS		1.9
Varity_R		0.13
gMVP		0.51
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: rs372004247; hg19: chr6-112671102;