rs1458926

Positions:

• chr8-109258466-C-G

Variant summary

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

The NM_032869.4(NUDCD1):​c.1299+12539G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.36 in 151,654 control chromosomes in the GnomAD database, including 10,676 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 0.36 (10676 hom., cov: 31)
• Consequence: NUDCD1 NM_032869.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0570

Genes affected

NUDCD1 (HGNC:24306): (NudC domain containing 1) Predicted to be involved in immune system process. Located in cytosol and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.48 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NUDCD1	NM_032869.4	c.1299+12539G>C		intron_variant		ENST00000239690.9	NP_116258.2
NUDCD1	NM_001128211.2	c.1212+12539G>C		intron_variant			NP_001121683.1
NUDCD1	XM_047422330.1	c.1038+12539G>C		intron_variant			XP_047278286.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NUDCD1	ENST00000239690.9	c.1299+12539G>C		intron_variant		1	NM_032869.4	ENSP00000239690	P1

Frequencies

GnomAD3 genomes AF: 0.361 AC: 54638 AN: 151536 Hom.: 10670 Cov.: 31

Gnomad AFR AF: 0.216

Gnomad AMI AF: 0.576

Gnomad AMR AF: 0.450

Gnomad ASJ AF: 0.252

Gnomad EAS AF: 0.471

Gnomad SAS AF: 0.497

Gnomad FIN AF: 0.452

Gnomad MID AF: 0.223

Gnomad NFE AF: 0.400

Gnomad OTH AF: 0.339

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

GnomAD4 genome AF: 0.360 AC: 54657 AN: 151654 Hom.: 10676 Cov.: 31 AF XY: 0.366 AC XY: 27110 AN XY: 74056

Gnomad4 AFR AF: 0.216

Gnomad4 AMR AF: 0.450

Gnomad4 ASJ AF: 0.252

Gnomad4 EAS AF: 0.472

Gnomad4 SAS AF: 0.497

Gnomad4 FIN AF: 0.452

Gnomad4 NFE AF: 0.400

Gnomad4 OTH AF: 0.342

Alfa AF: 0.382 Hom.: 1461

Bravo AF: 0.351

Asia WGS AF: 0.502 AC: 1746 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.3
DANN	Benign	0.73

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: rs1458926; hg19: chr8-110270695; COSMIC: COSV53454631;