rs4945008

chr11-71510202-A-Gchr11-71510202-A-T

Variant summary

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

The ENST00000527963.1(NADSYN1):c.*74+8776A>G variant causes a intron, NMD transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.526 in 152,150 control chromosomes in the GnomAD database, including 25,135 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 0.53 (25135 hom., cov: 33)
• Consequence: NADSYN1 ENST00000527963.1 intron, NMD_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.164

Genes affected

NADSYN1 (HGNC:29832): (NAD synthetase 1) Nicotinamide adenine dinucleotide (NAD) is a coenzyme in metabolic redox reactions, a precursor for several cell signaling molecules, and a substrate for protein posttranslational modifications. NAD synthetase (EC 6.3.5.1) catalyzes the final step in the biosynthesis of NAD from nicotinic acid adenine dinucleotide (NaAD).[supplied by OMIM, Apr 2004]

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 (NFE) allele frequency at 95% confidence interval = 0.734 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NADSYN1	ENST00000527963.1	c.*74+8776A>G		intron_variant, NMD_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.526 AC: 80033 AN: 152030 Hom.: 25131 Cov.: 33

Gnomad AFR AF: 0.221

Gnomad AMI AF: 0.702

Gnomad AMR AF: 0.486

Gnomad ASJ AF: 0.610

Gnomad EAS AF: 0.381

Gnomad SAS AF: 0.208

Gnomad FIN AF: 0.588

Gnomad MID AF: 0.434

Gnomad NFE AF: 0.740

Gnomad OTH AF: 0.517

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

GnomAD4 genome AF: 0.526 AC: 80044 AN: 152150 Hom.: 25135 Cov.: 33 AF XY: 0.511 AC XY: 38013 AN XY: 74382

Gnomad4 AFR AF: 0.221

Gnomad4 AMR AF: 0.486

Gnomad4 ASJ AF: 0.610

Gnomad4 EAS AF: 0.382

Gnomad4 SAS AF: 0.210

Gnomad4 FIN AF: 0.588

Gnomad4 NFE AF: 0.740

Gnomad4 OTH AF: 0.511

Alfa AF: 0.560 Hom.: 3790

Bravo AF: 0.515

Asia WGS AF: 0.270 AC: 943 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	6.5
Dann	Benign	0.51

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs4945008; hg19: chr11-71221248;