dbSNP rs2304191: NMRK2:c.-215+56T>C (chr19-3933234-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0660

Publications

11 publications found

Variant links:

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]

NMRK2 links:

ENSG00000289254 (HGNC:):

ENSG00000289254 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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	Effect	Exon rank	MANE	Protein
NMRK2	NM_170678.3 link	c.-215+56T>C	intron_variant	Intron 1 of 7	ENST00000168977.7	NP_733778.1
NMRK2	NM_001289117.2 link	c.-215+56T>C	intron_variant	Intron 1 of 7		NP_001276046.1
NMRK2	NR_110316.2 link	n.110+56T>C	intron_variant	Intron 1 of 4
NMRK2	XM_006722725.4 link	c.-438T>C	upstream_gene_variant			XP_006722788.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NMRK2	ENST00000168977.7 link	c.-215+56T>C		intron_variant	Intron 1 of 7	2	NM_170678.3	ENSP00000168977.1

Frequencies

GnomAD3 genomes

AF:

0.170

AC:

25492

AN:

149712

Hom.:

3007

Cov.:

show subpopulations

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.:

AF XY:

0.0701

AC XY:

699

AN XY:

9976

show subpopulations

African (AFR)

AF:

0.259

AC:

119

AN:

460

American (AMR)

AF:

0.0574

AC:

AN:

1220

Ashkenazi Jewish (ASJ)

AF:

0.114

AC:

AN:

648

East Asian (EAS)

AF:

0.0183

AC:

AN:

930

South Asian (SAS)

AF:

0.0325

AC:

AN:

1632

European-Finnish (FIN)

AF:

0.0698

AC:

AN:

946

Middle Eastern (MID)

AF:

0.0588

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0743

AC:

900

AN:

12110

Other (OTH)

AF:

0.0787

AC:

AN:

1220

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

120

179

239

299

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.171

AC:

25553

AN:

149830

Hom.:

3024

Cov.:

AF XY:

0.165

AC XY:

12034

AN XY:

72984

show subpopulations

African (AFR)

AF:

0.343

AC:

13944

AN:

40678

American (AMR)

AF:

0.109

AC:

1613

AN:

14820

Ashkenazi Jewish (ASJ)

AF:

0.167

AC:

577

AN:

3460

East Asian (EAS)

AF:

0.0280

AC:

140

AN:

4994

South Asian (SAS)

AF:

0.0473

AC:

224

AN:

4732

European-Finnish (FIN)

AF:

0.0997

AC:

1019

AN:

10218

Middle Eastern (MID)

AF:

0.154

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.111

AC:

7505

AN:

67662

Other (OTH)

AF:

0.185

AC:

381

AN:

2064

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.514

Heterozygous variant carriers

971

1943

2914

3886

4857

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

260

520

780

1040

1300

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.123

Hom.:

2525

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

(source)

DANN

Benign

0.51

PhyloP100

-0.066

PromoterAI

0.068

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over