dbSNP rs143766228: ZFR:c.1713+6T>C (chr5-32400001-A-G) – ACMG Classification: Benign (-16 pts)

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_016107.5(ZFR):c.1713+6T>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00357 in 1,594,980 control chromosomes in the GnomAD database, including 18 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0033 ( 2 hom., cov: 33)

Exomes 𝑓: 0.0036 ( 16 hom. )

Consequence

ZFR
NM_016107.5 splice_region, intron

Scores

Splicing: ADA: 0.06319

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.29

Publications

0 publications found

Variant links:

Genes affected

ZFR (HGNC:17277): (zinc finger RNA binding protein) This gene encodes an RNA-binding protein characterized by its DZF (domain associated with zinc fingers) domain. The encoded protein may play a role in the nucleocytoplasmic shuttling of another RNA-binding protein, Staufen homolog 2, in neurons. Expression of this gene is regulated through alternative polyadenylation that mediates differential microRNA targeting. Elevated expression of this gene has been observed in human patients with pancreatic cancer and knockdown of this gene may result in reduced viability and invasion of pancreatic cancer cells. [provided by RefSeq, Sep 2016]

ZFR Gene-Disease associations (from GenCC):

autosomal recessive spastic paraplegia type 71
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
hereditary spastic paraplegia
Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ZFR links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.57).

BP6

Variant 5-32400001-A-G is Benign according to our data. Variant chr5-32400001-A-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 544265.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZFR	NM_016107.5 link	c.1713+6T>C		splice_region_variant, intron_variant	Intron 9 of 19	ENST00000265069.13	NP_057191.2	Q96KR1Q05D65
ZFR	NR_144318.2 link	n.1795+6T>C		splice_region_variant, intron_variant	Intron 9 of 18

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZFR	ENST00000265069.13 link	c.1713+6T>C		splice_region_variant, intron_variant	Intron 9 of 19	1	NM_016107.5	ENSP00000265069.8		Q96KR1

Frequencies

GnomAD3 genomes

AF:

0.00327

AC:

498

AN:

152188

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00177

Gnomad ASJ

AF:

0.0110

Gnomad EAS

AF:

0.000769

Gnomad SAS

AF:

0.000829

Gnomad FIN

AF:

0.00678

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00467

Gnomad OTH

AF:

0.00239

GnomAD2 exomes

AF:

0.00334

AC:

801

AN:

239894

AF XY:

0.00329

show subpopulations

Gnomad AFR exome

AF:

0.000317

Gnomad AMR exome

AF:

0.000850

Gnomad ASJ exome

AF:

0.00758

Gnomad EAS exome

AF:

0.000283

Gnomad FIN exome

AF:

0.00865

Gnomad NFE exome

AF:

0.00401

Gnomad OTH exome

AF:

0.00344

GnomAD4 exome

AF:

0.00360

AC:

5197

AN:

1442674

Hom.:

Cov.:

AF XY:

0.00356

AC XY:

2550

AN XY:

716936

show subpopulations

African (AFR)

AF:

0.000487

AC:

AN:

32856

American (AMR)

AF:

0.000996

AC:

AN:

42186

Ashkenazi Jewish (ASJ)

AF:

0.00778

AC:

199

AN:

25564

East Asian (EAS)

AF:

0.000435

AC:

AN:

39058

South Asian (SAS)

AF:

0.00191

AC:

159

AN:

83126

European-Finnish (FIN)

AF:

0.00796

AC:

416

AN:

52250

Middle Eastern (MID)

AF:

0.00405

AC:

AN:

5682

European-Non Finnish (NFE)

AF:

0.00371

AC:

4094

AN:

1102426

Other (OTH)

AF:

0.00388

AC:

231

AN:

59526

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

242

484

726

968

1210

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

148

296

444

592

740

<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:

0.00327

AC:

498

AN:

152306

Hom.:

Cov.:

AF XY:

0.00337

AC XY:

251

AN XY:

74476

show subpopulations

African (AFR)

AF:

0.000722

AC:

AN:

41562

American (AMR)

AF:

0.00177

AC:

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.0110

AC:

AN:

3470

East Asian (EAS)

AF:

0.000771

AC:

AN:

5190

South Asian (SAS)

AF:

0.000830

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00678

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00467

AC:

318

AN:

68032

Other (OTH)

AF:

0.00237

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

113

141

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<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:

0.00429

Hom.:

Bravo

AF:

0.00254

Asia WGS

AF:

0.00115

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Pure or complex autosomal recessive spastic paraplegia

Benign:1

Jan 22, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.57

CADD

Benign

(source)

DANN

Benign

0.76

PhyloP100

2.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=91/9

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.063

dbscSNV1_RF

Benign

0.19

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over