6-116592949-ATTTTT-ATTTTTT

Variant names:

• chr6-116592949-A-AT
• rs2243350
• NM_015952.4:c.611-16dupT

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_015952.4(RWDD1):​c.611-16dupT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.128 in 1,376,506 control chromosomes in the GnomAD database, including 1,124 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.12 (1027 hom., cov: 29)
  • Exomes 𝑓: 0.13 (97 hom.)
• Consequence: RWDD1 NM_015952.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0680
• 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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.183 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RWDD1	NM_015952.4	MANE Select	c.611-16dupT		intron	N/A	NP_057036.2	Q9H446-1
	RWDD1	NM_001007464.3		c.323-16dupT		intron	N/A	NP_001007465.1	Q9H446-2
	RWDD1	NM_016104.4		c.323-16dupT		intron	N/A	NP_057188.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RWDD1	ENST00000466444.7	TSL:1 MANE Select	c.611-31_611-30insT		intron	N/A	ENSP00000420357.2	Q9H446-1
	RWDD1	ENST00000487832.6	TSL:1	c.323-31_323-30insT		intron	N/A	ENSP00000428778.1	Q9H446-2

Frequencies

GnomAD3 genomes AF: 0.116 AC: 16485 AN: 141908 Hom.: 1024 Cov.: 29

Gnomad AFR AF: 0.150

Gnomad AMI AF: 0.0244

Gnomad AMR AF: 0.189

Gnomad ASJ AF: 0.108

Gnomad EAS AF: 0.0247

Gnomad SAS AF: 0.0813

Gnomad FIN AF: 0.0735

Gnomad MID AF: 0.0604

Gnomad NFE AF: 0.0966

Gnomad OTH AF: 0.113

GnomAD2 exomes AF: 0.140 AC: 20374 AN: 145910 AF XY: 0.134

Gnomad AFR exome AF: 0.188

Gnomad AMR exome AF: 0.238

Gnomad ASJ exome AF: 0.123

Gnomad EAS exome AF: 0.0809

Gnomad FIN exome AF: 0.0996

Gnomad NFE exome AF: 0.129

Gnomad OTH exome AF: 0.127

GnomAD4 exome AF: 0.130 AC: 160058 AN: 1234554 Hom.: 97 Cov.: 0 AF XY: 0.127 AC XY: 78284 AN XY: 617278

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.171 AC: 4757 AN: 27776

American (AMR) AF: 0.202 AC: 7003 AN: 34752

Ashkenazi Jewish (ASJ) AF: 0.124 AC: 2755 AN: 22266

East Asian (EAS) AF: 0.0688 AC: 2418 AN: 35162

South Asian (SAS) AF: 0.106 AC: 7672 AN: 72666

European-Finnish (FIN) AF: 0.0900 AC: 3878 AN: 43080

Middle Eastern (MID) AF: 0.0854 AC: 398 AN: 4662

European-Non Finnish (NFE) AF: 0.132 AC: 124520 AN: 942660

Other (OTH) AF: 0.129 AC: 6657 AN: 51530

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.116 AC: 16501 AN: 141952 Hom.: 1027 Cov.: 29 AF XY: 0.115 AC XY: 7899 AN XY: 68802

African (AFR) AF: 0.150 AC: 5839 AN: 38812

American (AMR) AF: 0.189 AC: 2689 AN: 14228

Ashkenazi Jewish (ASJ) AF: 0.108 AC: 360 AN: 3340

East Asian (EAS) AF: 0.0247 AC: 120 AN: 4852

South Asian (SAS) AF: 0.0817 AC: 361 AN: 4418

European-Finnish (FIN) AF: 0.0735 AC: 636 AN: 8652

Middle Eastern (MID) AF: 0.0576 AC: 16 AN: 278

European-Non Finnish (NFE) AF: 0.0966 AC: 6238 AN: 64562

Other (OTH) AF: 0.113 AC: 221 AN: 1950

Alfa AF: 0.0424 Hom.: 6

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.068
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: rs2243350; hg19: chr6-116914112;