rs11234027

Variant names:

• chr11-71523061-G-A
• rs11234027
• ENST00000527963.1:n.*190-935G>A

Variant summary

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

The ENST00000527963.1(NADSYN1):​n.*190-935G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.236 in 152,126 control chromosomes in the GnomAD database, including 4,734 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 0.24 (4734 hom., cov: 33)
• Consequence: NADSYN1 ENST00000527963.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.328
• Publications: 41 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=-0.7).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.322 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NADSYN1	ENST00000527963.1	n.*190-935G>A		intron_variant	Intron 3 of 3	4		ENSP00000435570.1

Frequencies

GnomAD3 genomes AF: 0.236 AC: 35822 AN: 152008 Hom.: 4711 Cov.: 33

Gnomad AFR AF: 0.320

Gnomad AMI AF: 0.282

Gnomad AMR AF: 0.262

Gnomad ASJ AF: 0.144

Gnomad EAS AF: 0.318

Gnomad SAS AF: 0.338

Gnomad FIN AF: 0.282

Gnomad MID AF: 0.285

Gnomad NFE AF: 0.161

Gnomad OTH AF: 0.258

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

GnomAD4 genome AF: 0.236 AC: 35876 AN: 152126 Hom.: 4734 Cov.: 33 AF XY: 0.246 AC XY: 18301 AN XY: 74360

African (AFR) AF: 0.321 AC: 13304 AN: 41484

American (AMR) AF: 0.261 AC: 3993 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.144 AC: 498 AN: 3468

East Asian (EAS) AF: 0.318 AC: 1646 AN: 5180

South Asian (SAS) AF: 0.335 AC: 1614 AN: 4812

European-Finnish (FIN) AF: 0.282 AC: 2984 AN: 10572

Middle Eastern (MID) AF: 0.265 AC: 78 AN: 294

European-Non Finnish (NFE) AF: 0.161 AC: 10950 AN: 68000

Other (OTH) AF: 0.261 AC: 552 AN: 2114

Alfa AF: 0.186 Hom.: 2020

Bravo AF: 0.234

Asia WGS AF: 0.311 AC: 1080 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	0.25
DANN	Benign	0.70
PhyloP100		-0.33

Splicing

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

Other links and lift over

dbSNP: rs11234027; hg19: chr11-71234107;