1-95237888-G-T

Variant names:

• chr1-95237888-G-T
• rs1160318
• NM_015485.5:c.85+3573G>T

Variant summary

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

The NM_015485.5(RWDD3):​c.85+3573G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.304 in 152,122 control chromosomes in the GnomAD database, including 7,336 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 0.30 (7336 hom., cov: 32)
• Consequence: RWDD3 NM_015485.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.231
• Publications: 5 publications found

Genes affected

RWDD3 (HGNC:21393): (RWD domain containing 3) Involved in negative regulation of NF-kappaB transcription factor activity; positive regulation of hypoxia-inducible factor-1alpha signaling pathway; and positive regulation of protein sumoylation. Predicted to be located in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

TLCD4-RWDD3 (HGNC:49388): (TLCD4-RWDD3 readthrough) This locus represents naturally occurring read-through transcription between the neighboring TMEM56 (transmembrane protein 56) and RWDD3 (RWD domain containing 3) genes on chromosome 1. The read-through transcript encodes a protein that shares sequence identity with the upstream gene product, but it contains a distinct C-terminus due to frameshifts versus the downstream gene coding sequence. [provided by RefSeq, Dec 2010]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.433 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RWDD3	NM_015485.5	c.85+3573G>T		intron_variant	Intron 1 of 3	ENST00000370202.5	NP_056300.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RWDD3	ENST00000370202.5	c.85+3573G>T		intron_variant	Intron 1 of 3	3	NM_015485.5	ENSP00000359221.4
TLCD4-RWDD3	ENST00000604534.5	c.567-6323G>T		intron_variant	Intron 7 of 7	2		ENSP00000475025.1

Frequencies

GnomAD3 genomes AF: 0.304 AC: 46207 AN: 152004 Hom.: 7321 Cov.: 32

Gnomad AFR AF: 0.363

Gnomad AMI AF: 0.249

Gnomad AMR AF: 0.259

Gnomad ASJ AF: 0.227

Gnomad EAS AF: 0.449

Gnomad SAS AF: 0.283

Gnomad FIN AF: 0.388

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.261

Gnomad OTH AF: 0.289

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

GnomAD4 genome AF: 0.304 AC: 46269 AN: 152122 Hom.: 7336 Cov.: 32 AF XY: 0.308 AC XY: 22893 AN XY: 74366

African (AFR) AF: 0.364 AC: 15094 AN: 41490

American (AMR) AF: 0.259 AC: 3956 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.227 AC: 789 AN: 3470

East Asian (EAS) AF: 0.449 AC: 2318 AN: 5166

South Asian (SAS) AF: 0.284 AC: 1371 AN: 4824

European-Finnish (FIN) AF: 0.388 AC: 4100 AN: 10572

Middle Eastern (MID) AF: 0.201 AC: 59 AN: 294

European-Non Finnish (NFE) AF: 0.261 AC: 17738 AN: 67986

Other (OTH) AF: 0.292 AC: 617 AN: 2114

Alfa AF: 0.270 Hom.: 22326

Bravo AF: 0.302

Asia WGS AF: 0.375 AC: 1301 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	10
DANN	Benign	0.78
PhyloP100		0.23
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: rs1160318; hg19: chr1-95703444;