chr11-71456989-A-G

Variant names:

• chr11-71456989-A-G
• rs4944957
• NM_018161.5:c.147-1439A>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.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
• Publications: 23 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=-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 rank	MANE	Protein	UniProt
NADSYN1	NM_018161.5	c.147-1439A>G		intron_variant	Intron 2 of 20	ENST00000319023.7	NP_060631.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NADSYN1	ENST00000319023.7	c.147-1439A>G		intron_variant	Intron 2 of 20	1	NM_018161.5	ENSP00000326424.2

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

African (AFR) AF: 0.506 AC: 21006 AN: 41500

American (AMR) AF: 0.512 AC: 7828 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.615 AC: 2134 AN: 3472

East Asian (EAS) AF: 0.381 AC: 1960 AN: 5138

South Asian (SAS) AF: 0.212 AC: 1023 AN: 4828

European-Finnish (FIN) AF: 0.589 AC: 6237 AN: 10596

Middle Eastern (MID) AF: 0.476 AC: 139 AN: 292

European-Non Finnish (NFE) AF: 0.744 AC: 50606 AN: 67992

Other (OTH) AF: 0.571 AC: 1204 AN: 2110

Alfa AF: 0.621 Hom.: 5134

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
PhyloP100		-0.40
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: rs4944957; hg19: chr11-71168035;