rs2238973

Positions:

• chrX-43954837-G-A

Variant summary

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

The NM_000266.4(NDP):​c.174+3635C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.49 in 109,499 control chromosomes in the GnomAD database, including 9,824 homozygotes. There are 15,164 hemizygotes in GnomAD. 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 0.49 (9824 hom., 15164 hem., cov: 22)
• Consequence: NDP NM_000266.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.302

Genes affected

NDP (HGNC:7678): (norrin cystine knot growth factor NDP) This gene encodes a secreted protein with a cystein-knot motif that activates the Wnt/beta-catenin pathway. The protein forms disulfide-linked oligomers in the extracellular matrix. Mutations in this gene result in Norrie disease and X-linked exudative vitreoretinopathy. [provided by RefSeq, Feb 2009]

NDP-AS1 (HGNC:40395): (NDP antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.623 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NDP	NM_000266.4	c.174+3635C>T		intron_variant		ENST00000642620.1	NP_000257.1
NDP-AS1	NR_046631.1	n.466+289G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NDP	ENST00000642620.1	c.174+3635C>T		intron_variant			NM_000266.4	ENSP00000495972	P1
NDP-AS1	ENST00000435093.1	n.466+289G>A		intron_variant, non_coding_transcript_variant		3
NDP	ENST00000647044.1	c.174+3635C>T		intron_variant				ENSP00000495811	P1
NDP	ENST00000470584.1	n.218+3881C>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.490 AC: 53591 AN: 109442 Hom.: 9818 Cov.: 22 AF XY: 0.476 AC XY: 15133 AN XY: 31778

Gnomad AFR AF: 0.631

Gnomad AMI AF: 0.503

Gnomad AMR AF: 0.475

Gnomad ASJ AF: 0.437

Gnomad EAS AF: 0.377

Gnomad SAS AF: 0.339

Gnomad FIN AF: 0.421

Gnomad MID AF: 0.453

Gnomad NFE AF: 0.437

Gnomad OTH AF: 0.483

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

GnomAD4 genome AF: 0.490 AC: 53619 AN: 109499 Hom.: 9824 Cov.: 22 AF XY: 0.476 AC XY: 15164 AN XY: 31845

Gnomad4 AFR AF: 0.630

Gnomad4 AMR AF: 0.475

Gnomad4 ASJ AF: 0.437

Gnomad4 EAS AF: 0.377

Gnomad4 SAS AF: 0.337

Gnomad4 FIN AF: 0.421

Gnomad4 NFE AF: 0.437

Gnomad4 OTH AF: 0.485

Alfa AF: 0.447 Hom.: 29518

Bravo AF: 0.502

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.77
DANN	Benign	0.40

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: rs2238973; hg19: chrX-43814083;