rs12649785

Positions:

• chr4-37334077-A-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001144990.2(NWD2):​c.240+8053A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.168 in 152,082 control chromosomes in the GnomAD database, including 2,548 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 0.17 (2548 hom., cov: 31)
• Consequence: NWD2 NM_001144990.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.342

Genes affected

NWD2 (HGNC:29229): (NACHT and WD repeat domain containing 2)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.349 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NWD2	NM_001144990.2	c.240+8053A>C		intron_variant		ENST00000309447.6	NP_001138462.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NWD2	ENST00000309447.6	c.240+8053A>C		intron_variant		5	NM_001144990.2	ENSP00000309501	P1

Frequencies

GnomAD3 genomes AF: 0.168 AC: 25572 AN: 151964 Hom.: 2542 Cov.: 31

Gnomad AFR AF: 0.151

Gnomad AMI AF: 0.262

Gnomad AMR AF: 0.293

Gnomad ASJ AF: 0.168

Gnomad EAS AF: 0.362

Gnomad SAS AF: 0.243

Gnomad FIN AF: 0.119

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.137

Gnomad OTH AF: 0.173

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

GnomAD4 genome AF: 0.168 AC: 25622 AN: 152082 Hom.: 2548 Cov.: 31 AF XY: 0.172 AC XY: 12786 AN XY: 74340

Gnomad4 AFR AF: 0.152

Gnomad4 AMR AF: 0.294

Gnomad4 ASJ AF: 0.168

Gnomad4 EAS AF: 0.363

Gnomad4 SAS AF: 0.244

Gnomad4 FIN AF: 0.119

Gnomad4 NFE AF: 0.137

Gnomad4 OTH AF: 0.175

Alfa AF: 0.150 Hom.: 3912

Bravo AF: 0.183

Asia WGS AF: 0.283 AC: 983 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	4.5
DANN	Benign	0.55

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

Publications

LitVar

Other links and lift over

dbSNP: rs12649785; hg19: chr4-37335699;