chr4-183650986-C-T

Variant names:

• chr4-183650986-C-T
• rs140946722
• NM_152682.4:c.361G>A

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_152682.4(RWDD4):​c.361G>A​(p.Ala121Thr) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000079 in 1,608,090 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 18/24 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000072 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000080 (0 hom.)
• Consequence: RWDD4 NM_152682.4 missense, splice_region
• Scores: Splicing: ADA: 0.00003933
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.131
• Publications: 0 publications found

Genes affected

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

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.010046005).
• BP6: Variant 4-183650986-C-T is Benign according to our data. Variant chr4-183650986-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3791557.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152682.4. 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.361G>A	p.Ala121Thr	missense splice_region	Exon 4 of 8	NP_689895.2	Q6NW29-1
	RWDD4	NM_001307922.2		c.172G>A	p.Ala58Thr	missense splice_region	Exon 4 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.361G>A	p.Ala121Thr	missense splice_region	Exon 4 of 8	ENSP00000388920.2	Q6NW29-1
	RWDD4	ENST00000327570.13	TSL:3	c.361G>A	p.Ala121Thr	missense splice_region	Exon 4 of 7	ENSP00000332177.9	K4DI92
	RWDD4	ENST00000512740.1	TSL:5	c.172G>A	p.Ala58Thr	missense splice_region	Exon 3 of 7	ENSP00000423598.1	E7EV43

Frequencies

GnomAD3 genomes AF: 0.0000723 AC: 11 AN: 152104 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00115

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000133 AC: 33 AN: 248766 AF XY: 0.000164

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000293

Gnomad ASJ exome AF: 0.00150

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000709

Gnomad OTH exome AF: 0.000164

GnomAD4 exome AF: 0.0000797 AC: 116 AN: 1455868 Hom.: 0 Cov.: 31 AF XY: 0.0000898 AC XY: 65 AN XY: 723554

African (AFR) AF: 0.0000601 AC: 2 AN: 33270

American (AMR) AF: 0.0000451 AC: 2 AN: 44340

Ashkenazi Jewish (ASJ) AF: 0.00146 AC: 38 AN: 26018

East Asian (EAS) AF: 0.00 AC: 0 AN: 39606

South Asian (SAS) AF: 0.000176 AC: 15 AN: 85174

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53338

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4262

European-Non Finnish (NFE) AF: 0.0000478 AC: 53 AN: 1109786

Other (OTH) AF: 0.0000999 AC: 6 AN: 60074

GnomAD4 genome AF: 0.0000723 AC: 11 AN: 152222 Hom.: 0 Cov.: 33 AF XY: 0.0000806 AC XY: 6 AN XY: 74418

African (AFR) AF: 0.0000482 AC: 2 AN: 41532

American (AMR) AF: 0.000131 AC: 2 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00115 AC: 4 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10588

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68010

Other (OTH) AF: 0.00 AC: 0 AN: 2116

Alfa AF: 0.000270 Hom.: 0

Bravo AF: 0.0000642

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.000148 AC: 18

EpiCase AF: 0.0000546

EpiControl AF: 0.000119

ClinVar

ClinVar submissions

Significance: Likely benign

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	0.058
BayesDel_addAF	Benign	-0.62	T
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.13
DANN	Benign	0.77
DEOGEN2	Benign	0.0021	T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.052	N
LIST_S2	Benign	0.72	T
M_CAP	Benign	0.0079	T
MetaRNN	Benign	0.010	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.045	N
PhyloP100		-0.13
PrimateAI	Benign	0.27	T
PROVEAN	Benign	0.070	N
REVEL	Benign	0.046
Sift	Benign	0.51	T
Sift4G	Benign	0.47	T
Polyphen		0.0010	B
Vest4		0.076
MVP		0.38
MPC		0.27
ClinPred		0.012	T
GERP RS		-8.6
Varity_R		0.024
gMVP		0.18
Mutation Taster		=94/6	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000039
dbscSNV1_RF	Benign	0.068
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: rs140946722; hg19: chr4-184572139;