Genetic Variant ZPR1:c.892-100G>A (chr11-116783719-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.892-100G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.382 in 866,758 control chromosomes in the GnomAD database, including 66,815 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 0.33 ( 9416 hom., cov: 31)

Exomes 𝑓: 0.39 ( 57399 hom. )

Consequence

ZPR1
NM_003904.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.642

Publications

62 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=-0.84).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.431 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.892-100G>A		intron	N/A	NP_003895.1
	ZPR1	NM_001317086.2		c.730-100G>A		intron	N/A	NP_001304015.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
ZPR1	ENST00000227322.8	TSL:1 MANE Select	c.892-100G>A	intron	N/A	ENSP00000227322.3
ZPR1	ENST00000900046.1		c.922-100G>A	intron	N/A	ENSP00000570105.1
ZPR1	ENST00000900049.1		c.892-100G>A	intron	N/A	ENSP00000570108.1

Frequencies

GnomAD3 genomes

AF:

0.332

AC:

50415

AN:

151752

Hom.:

9424

Cov.:

show subpopulations

Gnomad AFR

AF:

0.184

Gnomad AMI

AF:

0.392

Gnomad AMR

AF:

0.278

Gnomad ASJ

AF:

0.399

Gnomad EAS

AF:

0.281

Gnomad SAS

AF:

0.264

Gnomad FIN

AF:

0.358

Gnomad MID

AF:

0.301

Gnomad NFE

AF:

0.435

Gnomad OTH

AF:

0.333

GnomAD4 exome

AF:

0.392

AC:

280346

AN:

714886

Hom.:

57399

AF XY:

0.389

AC XY:

147523

AN XY:

379720

show subpopulations

African (AFR)

AF:

0.182

AC:

3319

AN:

18248

American (AMR)

AF:

0.252

AC:

8009

AN:

31814

Ashkenazi Jewish (ASJ)

AF:

0.408

AC:

7442

AN:

18262

East Asian (EAS)

AF:

0.244

AC:

8802

AN:

36024

South Asian (SAS)

AF:

0.272

AC:

17223

AN:

63314

European-Finnish (FIN)

AF:

0.363

AC:

17165

AN:

47256

Middle Eastern (MID)

AF:

0.268

AC:

1121

AN:

4176

European-Non Finnish (NFE)

AF:

0.443

AC:

203858

AN:

460370

Other (OTH)

AF:

0.378

AC:

13407

AN:

35422

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

7825

15651

23476

31302

39127

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3186

6372

9558

12744

15930

<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:

0.332

AC:

50404

AN:

151872

Hom.:

9416

Cov.:

AF XY:

0.324

AC XY:

24028

AN XY:

74232

show subpopulations

African (AFR)

AF:

0.184

AC:

7630

AN:

41398

American (AMR)

AF:

0.277

AC:

4229

AN:

15260

Ashkenazi Jewish (ASJ)

AF:

0.399

AC:

1386

AN:

3472

East Asian (EAS)

AF:

0.279

AC:

1442

AN:

5164

South Asian (SAS)

AF:

0.264

AC:

1264

AN:

4796

European-Finnish (FIN)

AF:

0.358

AC:

3776

AN:

10546

Middle Eastern (MID)

AF:

0.303

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.435

AC:

29540

AN:

67932

Other (OTH)

AF:

0.329

AC:

692

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1561

3123

4684

6246

7807

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

502

1004

1506

2008

2510

<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:

0.351

Hom.:

4005

Bravo

AF:

0.322

Asia WGS

AF:

0.244

AC:

851

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

7.5

(source)

DANN

Benign

0.41

PhyloP100

-0.64

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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