11-71456989-A-G

Position:

• chr11-71456989-A-G

Variant summary

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

The NM_018161.5(NADSYN1):​c.147-1439A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.61 in 152,134 control chromosomes in the GnomAD database, including 29,921 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 0.61 (29921 hom., cov: 34)
• Consequence: NADSYN1 NM_018161.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.398

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=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.739 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NADSYN1	NM_018161.5	c.147-1439A>G		intron_variant		ENST00000319023.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NADSYN1	ENST00000319023.7	c.147-1439A>G		intron_variant		1	NM_018161.5	P1

Frequencies

GnomAD3 genomes AF: 0.610 AC: 92673 AN: 152014 Hom.: 29878 Cov.: 34

Gnomad AFR AF: 0.505

Gnomad AMI AF: 0.689

Gnomad AMR AF: 0.512

Gnomad ASJ AF: 0.615

Gnomad EAS AF: 0.381

Gnomad SAS AF: 0.210

Gnomad FIN AF: 0.589

Gnomad MID AF: 0.459

Gnomad NFE AF: 0.744

Gnomad OTH AF: 0.577

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

GnomAD4 genome AF: 0.610 AC: 92764 AN: 152134 Hom.: 29921 Cov.: 34 AF XY: 0.592 AC XY: 44046 AN XY: 74390

Gnomad4 AFR AF: 0.506

Gnomad4 AMR AF: 0.512

Gnomad4 ASJ AF: 0.615

Gnomad4 EAS AF: 0.381

Gnomad4 SAS AF: 0.212

Gnomad4 FIN AF: 0.589

Gnomad4 NFE AF: 0.744

Gnomad4 OTH AF: 0.571

Alfa AF: 0.626 Hom.: 5042

Bravo AF: 0.609

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.52
DANN	Benign	0.30

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: rs4944957; hg19: chr11-71168035;