11-71456403-G-T

Position:

• chr11-71456403-G-T

Variant summary

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

The ENST00000319023.7(NADSYN1):​c.146+1233G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.535 in 152,022 control chromosomes in the GnomAD database, including 25,588 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 0.54 (25588 hom., cov: 33)
• Consequence: NADSYN1 ENST00000319023.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.340

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=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.738 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NADSYN1	NM_018161.5	c.146+1233G>T		intron_variant		ENST00000319023.7	NP_060631.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NADSYN1	ENST00000319023.7	c.146+1233G>T		intron_variant		1	NM_018161.5	ENSP00000326424	P1

Frequencies

GnomAD3 genomes AF: 0.536 AC: 81387 AN: 151902 Hom.: 25585 Cov.: 33

Gnomad AFR AF: 0.248

Gnomad AMI AF: 0.688

Gnomad AMR AF: 0.485

Gnomad ASJ AF: 0.615

Gnomad EAS AF: 0.383

Gnomad SAS AF: 0.209

Gnomad FIN AF: 0.589

Gnomad MID AF: 0.446

Gnomad NFE AF: 0.743

Gnomad OTH AF: 0.527

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

GnomAD4 genome AF: 0.535 AC: 81401 AN: 152022 Hom.: 25588 Cov.: 33 AF XY: 0.520 AC XY: 38624 AN XY: 74312

Gnomad4 AFR AF: 0.247

Gnomad4 AMR AF: 0.485

Gnomad4 ASJ AF: 0.615

Gnomad4 EAS AF: 0.383

Gnomad4 SAS AF: 0.211

Gnomad4 FIN AF: 0.589

Gnomad4 NFE AF: 0.743

Gnomad4 OTH AF: 0.521

Alfa AF: 0.700 Hom.: 47221

Bravo AF: 0.525

Asia WGS AF: 0.274 AC: 957 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.058
DANN	Benign	0.35

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: rs12785878; hg19: chr11-71167449;