chr11-71454579-A-G

Variant names:

• chr11-71454579-A-G
• rs7944926
• NM_018161.5:c.86-531A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018161.5(NADSYN1):​c.86-531A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.538 in 150,324 control chromosomes in the GnomAD database, including 25,312 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 (25312 hom., cov: 33)
• Consequence: NADSYN1 NM_018161.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.628
• Publications: 76 publications found

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]

NADSYN1 Gene-Disease associations (from GenCC):

• vertebral, cardiac, renal, and limb defects syndrome 3

  Inheritance: AR Classification: STRONG, MODERATE, LIMITED Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)
• congenital vertebral-cardiac-renal anomalies syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.737 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NADSYN1	NM_018161.5	c.86-531A>G		intron_variant	Intron 1 of 20	ENST00000319023.7	NP_060631.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NADSYN1	ENST00000319023.7	c.86-531A>G		intron_variant	Intron 1 of 20	1	NM_018161.5	ENSP00000326424.2

Frequencies

GnomAD3 genomes AF: 0.538 AC: 80842 AN: 150232 Hom.: 25308 Cov.: 33

Gnomad AFR AF: 0.254

Gnomad AMI AF: 0.682

Gnomad AMR AF: 0.484

Gnomad ASJ AF: 0.613

Gnomad EAS AF: 0.379

Gnomad SAS AF: 0.210

Gnomad FIN AF: 0.586

Gnomad MID AF: 0.432

Gnomad NFE AF: 0.742

Gnomad OTH AF: 0.525

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

GnomAD4 genome AF: 0.538 AC: 80859 AN: 150324 Hom.: 25312 Cov.: 33 AF XY: 0.522 AC XY: 38310 AN XY: 73414

African (AFR) AF: 0.254 AC: 10219 AN: 40244

American (AMR) AF: 0.484 AC: 7369 AN: 15234

Ashkenazi Jewish (ASJ) AF: 0.613 AC: 2117 AN: 3456

East Asian (EAS) AF: 0.380 AC: 1949 AN: 5130

South Asian (SAS) AF: 0.212 AC: 1021 AN: 4824

European-Finnish (FIN) AF: 0.586 AC: 6143 AN: 10488

Middle Eastern (MID) AF: 0.455 AC: 131 AN: 288

European-Non Finnish (NFE) AF: 0.742 AC: 50210 AN: 67666

Other (OTH) AF: 0.519 AC: 1089 AN: 2098

Alfa AF: 0.672 Hom.: 59228

Bravo AF: 0.525

Asia WGS AF: 0.273 AC: 954 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.1
DANN	Benign	0.63
PhyloP100		-0.63
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7944926; hg19: chr11-71165625;