4-183658948-C-T

Variant names:

• chr4-183658948-C-T
• rs761086916
• NM_152682.4:c.5G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001307922.2(RWDD4):​c.-181G>A variant causes a 5 prime UTR premature start codon gain change. The variant allele was found at a frequency of 0.00000392 in 1,275,112 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000036 (0 hom.)
• Consequence: RWDD4 NM_001307922.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.36
• Publications: 5 publications found

Genes affected

RWDD4 (HGNC:23750): (RWD domain containing 4)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.18415487).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001307922.2. 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
	RWDD4	NM_152682.4	MANE Select	c.5G>A	p.Ser2Asn	missense	Exon 1 of 8	NP_689895.2	Q6NW29-1
	RWDD4	NM_001307922.2		c.-181G>A		5_prime_UTR_premature_start_codon_gain	Exon 1 of 8	NP_001294851.1	E7EV43
	RWDD4	NM_001307922.2		c.-181G>A		5_prime_UTR	Exon 1 of 8	NP_001294851.1	E7EV43

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RWDD4	ENST00000326397.10	TSL:2 MANE Select	c.5G>A	p.Ser2Asn	missense	Exon 1 of 8	ENSP00000388920.2	Q6NW29-1
	RWDD4	ENST00000512740.1	TSL:5	c.-100G>A		5_prime_UTR_premature_start_codon_gain	Exon 1 of 7	ENSP00000423598.1	E7EV43
	RWDD4	ENST00000510968.5	TSL:4	c.-90G>A		5_prime_UTR_premature_start_codon_gain	Exon 1 of 6	ENSP00000426329.1	Q6NW29-2

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152204 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

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: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000156 AC: 1 AN: 63952 AF XY: 0.0000272

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: 0.00

Gnomad NFE exome AF: 0.0000267

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000356 AC: 4 AN: 1122908 Hom.: 0 Cov.: 30 AF XY: 0.00000374 AC XY: 2 AN XY: 535338

African (AFR) AF: 0.00 AC: 0 AN: 24504

American (AMR) AF: 0.00 AC: 0 AN: 14612

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14866

East Asian (EAS) AF: 0.00 AC: 0 AN: 29470

South Asian (SAS) AF: 0.00 AC: 0 AN: 23606

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 23890

Middle Eastern (MID) AF: 0.000337 AC: 1 AN: 2966

European-Non Finnish (NFE) AF: 0.00000212 AC: 2 AN: 943802

Other (OTH) AF: 0.0000221 AC: 1 AN: 45192

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152204 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74358

African (AFR) AF: 0.00 AC: 0 AN: 41454

American (AMR) AF: 0.00 AC: 0 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4838

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68030

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

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ExAC AF: 0.00000955 AC: 1

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	0.21
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0053	T
Eigen	Benign	-0.13
Eigen_PC	Benign	0.0082
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Benign	0.68	T
M_CAP	Benign	0.030	D
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.99	L
PhyloP100		4.4
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	-0.97	N
REVEL	Benign	0.045
Sift	Benign	0.083	T
Sift4G	Benign	0.31	T
Polyphen		0.35	B
Vest4		0.15
MutPred		0.40		Gain of glycosylation at S2 (P = 0.0135)
MVP		0.47
MPC		0.30
ClinPred		0.54	D
GERP RS		4.2
PromoterAI		-0.0066	Neutral
Varity_R		0.15
gMVP		0.13
Mutation Taster		=92/8	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: rs761086916; hg19: chr4-184580101;