rs1998166

Variant names:

• chr6-116592254-T-C
• rs1998166
• NM_015952.4:c.611-726T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015952.4(RWDD1):​c.611-726T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.109 in 152,232 control chromosomes in the GnomAD database, including 1,052 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.11 (1052 hom., cov: 32)
• Consequence: RWDD1 NM_015952.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.09
• Publications: 2 publications found

Genes affected

RWDD1 (HGNC:20993): (RWD domain containing 1) Predicted to be involved in several processes, including cellular response to lipid; cytoplasmic translation; and positive regulation of androgen receptor activity. Predicted to be located in cytoplasm. Predicted to be part of polysome. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.172 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015952.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RWDD1	NM_015952.4	MANE Select	c.611-726T>C		intron	N/A	NP_057036.2
	RWDD1	NM_001007464.3		c.323-726T>C		intron	N/A	NP_001007465.1
	RWDD1	NM_016104.4		c.323-726T>C		intron	N/A	NP_057188.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RWDD1	ENST00000466444.7	TSL:1 MANE Select	c.611-726T>C		intron	N/A	ENSP00000420357.2
	RWDD1	ENST00000487832.6	TSL:1	c.323-726T>C		intron	N/A	ENSP00000428778.1

Frequencies

GnomAD3 genomes AF: 0.109 AC: 16584 AN: 152114 Hom.: 1049 Cov.: 32

Gnomad AFR AF: 0.143

Gnomad AMI AF: 0.0230

Gnomad AMR AF: 0.177

Gnomad ASJ AF: 0.0757

Gnomad EAS AF: 0.0210

Gnomad SAS AF: 0.0752

Gnomad FIN AF: 0.0698

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0915

Gnomad OTH AF: 0.105

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.109 AC: 16599 AN: 152232 Hom.: 1052 Cov.: 32 AF XY: 0.107 AC XY: 7984 AN XY: 74434

African (AFR) AF: 0.143 AC: 5938 AN: 41530

American (AMR) AF: 0.177 AC: 2708 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0757 AC: 263 AN: 3472

East Asian (EAS) AF: 0.0212 AC: 110 AN: 5182

South Asian (SAS) AF: 0.0752 AC: 362 AN: 4812

European-Finnish (FIN) AF: 0.0698 AC: 741 AN: 10612

Middle Eastern (MID) AF: 0.0476 AC: 14 AN: 294

European-Non Finnish (NFE) AF: 0.0915 AC: 6223 AN: 68014

Other (OTH) AF: 0.104 AC: 219 AN: 2114

Alfa AF: 0.102 Hom.: 1180

Bravo AF: 0.122

Asia WGS AF: 0.0550 AC: 192 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.37
DANN	Benign	0.63
PhyloP100		-3.1
Mutation Taster		=100/0	polymorphism (auto)

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: rs1998166; hg19: chr6-116913417;