9-75068110-T-C

Variant names:

• chr9-75068110-T-C
• rs7021664
• NM_017881.3:c.496+886A>G

Variant summary

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

The NM_017881.3(NMRK1):​c.496+886A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.944 in 152,186 control chromosomes in the GnomAD database, including 67,842 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 0.94 (67842 hom., cov: 30)
• Consequence: NMRK1 NM_017881.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.603

Genes affected

NMRK1 (HGNC:26057): (nicotinamide riboside kinase 1) Nicotinamide adenine dinucleotide (NAD+) is essential for life in all organisms, both as a coenzyme for oxidoreductases and as a source of ADP-ribosyl groups used in various reactions. Nicotinic acid and nicotinamide, collectively known as niacin, are the vitamin precursors of NAD+. Nicotinamide riboside kinases, such as NRK1, function to synthesize NAD+ through nicotinamide mononucleotide using nicotinamide riboside as the precursor (Bieganowski and Brenner, 2004 [PubMed 15137942]).[supplied by OMIM, Mar 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NMRK1	NM_017881.3	c.496+886A>G		intron_variant	Intron 7 of 8	ENST00000361092.9	NP_060351.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NMRK1	ENST00000361092.9	c.496+886A>G		intron_variant	Intron 7 of 8	1	NM_017881.3	ENSP00000354387.4
NMRK1	ENST00000376808.8	c.424+886A>G		intron_variant	Intron 6 of 7	1		ENSP00000366004.4
NMRK1	ENST00000376811.5	c.508+886A>G		intron_variant	Intron 8 of 9	2		ENSP00000366007.1
NMRK1	ENST00000494066.1	n.*895+886A>G		intron_variant	Intron 5 of 6	2		ENSP00000435736.1

Frequencies

GnomAD3 genomes AF: 0.944 AC: 143494 AN: 152068 Hom.: 67785 Cov.: 30

Gnomad AFR AF: 0.982

Gnomad AMI AF: 0.920

Gnomad AMR AF: 0.947

Gnomad ASJ AF: 0.913

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.916

Gnomad FIN AF: 0.905

Gnomad MID AF: 0.915

Gnomad NFE AF: 0.925

Gnomad OTH AF: 0.936

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

GnomAD4 genome AF: 0.944 AC: 143611 AN: 152186 Hom.: 67842 Cov.: 30 AF XY: 0.943 AC XY: 70101 AN XY: 74376

Gnomad4 AFR AF: 0.982

Gnomad4 AMR AF: 0.946

Gnomad4 ASJ AF: 0.913

Gnomad4 EAS AF: 0.999

Gnomad4 SAS AF: 0.915

Gnomad4 FIN AF: 0.905

Gnomad4 NFE AF: 0.925

Gnomad4 OTH AF: 0.936

Alfa AF: 0.928 Hom.: 82285

Bravo AF: 0.950

Asia WGS AF: 0.964 AC: 3352 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.79
DANN	Benign	0.65

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: rs7021664; hg19: chr9-77683026;