rs4945007

Positions:

• chr11-71509138-C-T

Variant summary

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

The ENST00000527963.1(NADSYN1):​c.*74+7712C>T variant causes a intron, NMD transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.891 in 152,338 control chromosomes in the GnomAD database, including 60,987 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 0.89 (60987 hom., cov: 34)
• Consequence: NADSYN1 ENST00000527963.1 intron, NMD_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.26

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=-0.99).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.948 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NADSYN1	ENST00000527963.1	c.*74+7712C>T		intron_variant, NMD_transcript_variant		4		ENSP00000435570

Frequencies

GnomAD3 genomes AF: 0.891 AC: 135687 AN: 152220 Hom.: 60951 Cov.: 34

Gnomad AFR AF: 0.838

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.813

Gnomad ASJ AF: 0.837

Gnomad EAS AF: 0.844

Gnomad SAS AF: 0.670

Gnomad FIN AF: 0.945

Gnomad MID AF: 0.831

Gnomad NFE AF: 0.954

Gnomad OTH AF: 0.893

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

GnomAD4 genome AF: 0.891 AC: 135774 AN: 152338 Hom.: 60987 Cov.: 34 AF XY: 0.887 AC XY: 66064 AN XY: 74496

Gnomad4 AFR AF: 0.838

Gnomad4 AMR AF: 0.813

Gnomad4 ASJ AF: 0.837

Gnomad4 EAS AF: 0.844

Gnomad4 SAS AF: 0.670

Gnomad4 FIN AF: 0.945

Gnomad4 NFE AF: 0.954

Gnomad4 OTH AF: 0.890

Alfa AF: 0.915 Hom.: 27016

Bravo AF: 0.880

Asia WGS AF: 0.700 AC: 2434 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.1
DANN	Benign	0.37

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4945007; hg19: chr11-71220184;