Genetic Variant ZPR1:c.424+124G>A (chr11-116786845-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_003904.5(ZPR1):c.424+124G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.743 in 818,886 control chromosomes in the GnomAD database, including 230,058 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 0.72 ( 40541 hom., cov: 33)

Exomes 𝑓: 0.75 ( 189517 hom. )

Consequence

ZPR1
NM_003904.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.152

Publications

64 publications found

Variant links:

Genes affected

ZPR1 (HGNC:13051): (ZPR1 zinc finger) The protein encoded by this gene is found in the cytoplasm of quiescent cells but translocates to the nucleolus in proliferating cells. The encoded protein interacts with survival motor neuron protein (SMN1) to enhance pre-mRNA splicing and to induce neuronal differentiation and axonal growth. Defects in this gene or the SMN1 gene can cause spinal muscular atrophy. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2015]

ZPR1 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=-0.76).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.791 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003904.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZPR1	NM_003904.5	MANE Select	c.424+124G>A		intron	N/A	NP_003895.1	O75312
	ZPR1	NM_001317086.2		c.262+124G>A		intron	N/A	NP_001304015.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ZPR1	ENST00000227322.8	TSL:1 MANE Select	c.424+124G>A	intron	N/A	ENSP00000227322.3	O75312
ZPR1	ENST00000900046.1		c.454+124G>A	intron	N/A	ENSP00000570105.1
ZPR1	ENST00000900049.1		c.424+124G>A	intron	N/A	ENSP00000570108.1

Frequencies

GnomAD3 genomes

AF:

0.724

AC:

110053

AN:

151940

Hom.:

40528

Cov.:

show subpopulations

Gnomad AFR

AF:

0.663

Gnomad AMI

AF:

0.721

Gnomad AMR

AF:

0.596

Gnomad ASJ

AF:

0.756

Gnomad EAS

AF:

0.591

Gnomad SAS

AF:

0.670

Gnomad FIN

AF:

0.769

Gnomad MID

AF:

0.661

Gnomad NFE

AF:

0.797

Gnomad OTH

AF:

0.707

GnomAD4 exome

AF:

0.747

AC:

498278

AN:

666828

Hom.:

189517

AF XY:

0.747

AC XY:

263938

AN XY:

353194

show subpopulations

African (AFR)

AF:

0.666

AC:

11627

AN:

17448

American (AMR)

AF:

0.512

AC:

18218

AN:

35584

Ashkenazi Jewish (ASJ)

AF:

0.763

AC:

13283

AN:

17412

East Asian (EAS)

AF:

0.514

AC:

18468

AN:

35930

South Asian (SAS)

AF:

0.671

AC:

40183

AN:

59876

European-Finnish (FIN)

AF:

0.763

AC:

36467

AN:

47766

Middle Eastern (MID)

AF:

0.696

AC:

1749

AN:

2512

European-Non Finnish (NFE)

AF:

0.800

AC:

333346

AN:

416706

Other (OTH)

AF:

0.742

AC:

24937

AN:

33594

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

6364

12729

19093

25458

31822

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3546

7092

10638

14184

17730

<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:

0.724

AC:

110104

AN:

152058

Hom.:

40541

Cov.:

AF XY:

0.717

AC XY:

53281

AN XY:

74328

show subpopulations

African (AFR)

AF:

0.663

AC:

27448

AN:

41426

American (AMR)

AF:

0.595

AC:

9092

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.756

AC:

2624

AN:

3472

East Asian (EAS)

AF:

0.590

AC:

3049

AN:

5170

South Asian (SAS)

AF:

0.668

AC:

3224

AN:

4824

European-Finnish (FIN)

AF:

0.769

AC:

8131

AN:

10574

Middle Eastern (MID)

AF:

0.660

AC:

194

AN:

294

European-Non Finnish (NFE)

AF:

0.797

AC:

54199

AN:

68004

Other (OTH)

AF:

0.704

AC:

1485

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1508

3016

4525

6033

7541

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

834

1668

2502

3336

4170

<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:

0.756

Hom.:

83110

Bravo

AF:

0.709

Asia WGS

AF:

0.603

AC:

2099

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

CADD

Benign

7.3

(source)

DANN

Benign

0.71

PhyloP100

0.15

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