dbSNP rs16846649: NVL:c.131+121A>G (chr1-224326270-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_002533.4(NVL):c.131+121A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0747 in 650,174 control chromosomes in the GnomAD database, including 2,155 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 0.061 ( 359 hom., cov: 32)

Exomes 𝑓: 0.079 ( 1796 hom. )

Consequence

NVL
NM_002533.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.08

Publications

6 publications found

Variant links:

Genes affected

NVL (HGNC:8070): (nuclear VCP like) This gene encodes a member of the AAA (ATPases associated with diverse cellular activities) superfamily. Multiple transcript variants encoding different isoforms have been found for this gene. Two encoded proteins, described as major and minor isoforms, have been localized to distinct regions of the nucleus. The largest encoded protein (major isoform) has been localized to the nucleolus and shown to participate in ribosome biosynthesis (PMID: 15469983, 16782053), while the minor isoform has been localized to the nucleoplasmin. [provided by RefSeq, Aug 2011]

NVL links:

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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=-0.68).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0992 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002533.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
NVL	NM_002533.4	MANE Select	c.131+121A>G	intron	N/A	NP_002524.2
NVL	NM_001243147.2		c.131+121A>G	intron	N/A	NP_001230076.1	O15381-5
NVL	NM_206840.3		c.-188+3801A>G	intron	N/A	NP_996671.1	O15381-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
NVL	ENST00000281701.11	TSL:1 MANE Select	c.131+121A>G	intron	N/A	ENSP00000281701.6	O15381-1
NVL	ENST00000391875.6	TSL:1	c.-188+3801A>G	intron	N/A	ENSP00000375747.2	O15381-2
NVL	ENST00000933815.1		c.131+121A>G	intron	N/A	ENSP00000603874.1

Frequencies

GnomAD3 genomes

AF:

0.0607

AC:

9236

AN:

152162

Hom.:

360

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0139

Gnomad AMI

AF:

0.0197

Gnomad AMR

AF:

0.0396

Gnomad ASJ

AF:

0.0620

Gnomad EAS

AF:

0.0494

Gnomad SAS

AF:

0.107

Gnomad FIN

AF:

0.0796

Gnomad MID

AF:

0.0443

Gnomad NFE

AF:

0.0896

Gnomad OTH

AF:

0.0478

GnomAD4 exome

AF:

0.0790

AC:

39321

AN:

497894

Hom.:

1796

AF XY:

0.0813

AC XY:

21485

AN XY:

264216

show subpopulations

African (AFR)

AF:

0.0136

AC:

190

AN:

13948

American (AMR)

AF:

0.0311

AC:

650

AN:

20886

Ashkenazi Jewish (ASJ)

AF:

0.0603

AC:

870

AN:

14430

East Asian (EAS)

AF:

0.0420

AC:

1409

AN:

33538

South Asian (SAS)

AF:

0.117

AC:

5069

AN:

43234

European-Finnish (FIN)

AF:

0.0801

AC:

3245

AN:

40514

Middle Eastern (MID)

AF:

0.0603

AC:

178

AN:

2950

European-Non Finnish (NFE)

AF:

0.0856

AC:

25758

AN:

300920

Other (OTH)

AF:

0.0710

AC:

1952

AN:

27474

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1678

3356

5035

6713

8391

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

248

496

744

992

1240

<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:

0.0607

AC:

9237

AN:

152280

Hom.:

359

Cov.:

AF XY:

0.0618

AC XY:

4604

AN XY:

74466

show subpopulations

African (AFR)

AF:

0.0138

AC:

574

AN:

41560

American (AMR)

AF:

0.0395

AC:

604

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.0620

AC:

215

AN:

3470

East Asian (EAS)

AF:

0.0495

AC:

257

AN:

5190

South Asian (SAS)

AF:

0.107

AC:

516

AN:

4830

European-Finnish (FIN)

AF:

0.0796

AC:

844

AN:

10604

Middle Eastern (MID)

AF:

0.0510

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0896

AC:

6093

AN:

68014

Other (OTH)

AF:

0.0477

AC:

101

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

437

874

1312

1749

2186

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

112

224

336

448

560

<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:

0.0578

Hom.:

191

Bravo

AF:

0.0533

Asia WGS

AF:

0.0520

AC:

180

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.68

CADD

Benign

6.1

(source)

DANN

Benign

0.90

PhyloP100

-1.1

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over