rs2304191

Positions:

• chr19-3933234-T-C
• chr19-3933234-T-G

Variant summary

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

The NM_170678.3(NMRK2):​c.-215+56T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.159 in 169,064 control chromosomes in the GnomAD database, including 3,127 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 0.17 (3024 hom., cov: 29)
  • Exomes 𝑓: 0.073 (103 hom.)
• Consequence: NMRK2 NM_170678.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0660

Genes affected

NMRK2 (HGNC:17871): (nicotinamide riboside kinase 2) Enables ribosylnicotinamide kinase activity and ribosylnicotinate kinase activity. Predicted to be involved in NAD metabolic process. Predicted to act upstream of or within negative regulation of myoblast differentiation. Located in nucleoplasm and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.338 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NMRK2	NM_170678.3	c.-215+56T>C		intron_variant		ENST00000168977.7	NP_733778.1
NMRK2	NM_001289117.2	c.-215+56T>C		intron_variant			NP_001276046.1
NMRK2	NR_110316.2	n.110+56T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NMRK2	ENST00000168977.7	c.-215+56T>C		intron_variant		2	NM_170678.3	ENSP00000168977	A2
	ENST00000691552.1	n.98-390A>G		intron_variant, non_coding_transcript_variant
NMRK2	ENST00000599576.5	c.-2+56T>C		intron_variant		3		ENSP00000471436
NMRK2	ENST00000616156.4	c.-215+56T>C		intron_variant		5		ENSP00000480091	P2

Frequencies

GnomAD3 genomes AF: 0.170 AC: 25492 AN: 149712 Hom.: 3007 Cov.: 29

Gnomad AFR AF: 0.343

Gnomad AMI AF: 0.115

Gnomad AMR AF: 0.109

Gnomad ASJ AF: 0.167

Gnomad EAS AF: 0.0282

Gnomad SAS AF: 0.0471

Gnomad FIN AF: 0.0997

Gnomad MID AF: 0.162

Gnomad NFE AF: 0.111

Gnomad OTH AF: 0.178

GnomAD4 exome AF: 0.0727 AC: 1399 AN: 19234 Hom.: 103 Cov.: 0 AF XY: 0.0701 AC XY: 699 AN XY: 9976

Gnomad4 AFR exome AF: 0.259

Gnomad4 AMR exome AF: 0.0574

Gnomad4 ASJ exome AF: 0.114

Gnomad4 EAS exome AF: 0.0183

Gnomad4 SAS exome AF: 0.0325

Gnomad4 FIN exome AF: 0.0698

Gnomad4 NFE exome AF: 0.0743

Gnomad4 OTH exome AF: 0.0787

GnomAD4 genome AF: 0.171 AC: 25553 AN: 149830 Hom.: 3024 Cov.: 29 AF XY: 0.165 AC XY: 12034 AN XY: 72984

Gnomad4 AFR AF: 0.343

Gnomad4 AMR AF: 0.109

Gnomad4 ASJ AF: 0.167

Gnomad4 EAS AF: 0.0280

Gnomad4 SAS AF: 0.0473

Gnomad4 FIN AF: 0.0997

Gnomad4 NFE AF: 0.111

Gnomad4 OTH AF: 0.185

Alfa AF: 0.120 Hom.: 1811

Bravo AF: 0.179

Asia WGS AF: 0.0870 AC: 304 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	11
DANN	Benign	0.51

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: rs2304191; hg19: chr19-3933232;