dbSNP rs7988: GZF1:c.*1607C>A (chr20-23372048-C-A) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_022482.5(GZF1):c.*1607C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.289 in 152,454 control chromosomes in the GnomAD database, including 6,458 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 0.29 ( 6446 hom., cov: 33)

Exomes 𝑓: 0.26 ( 12 hom. )

Consequence

GZF1
NM_022482.5 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.172

Publications

17 publications found

Variant links:

Genes affected

GZF1 (HGNC:15808): (GDNF inducible zinc finger protein 1) Enables DNA-binding transcription repressor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Involved in negative regulation of transcription by RNA polymerase II. Located in nucleolus and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

GZF1 Gene-Disease associations (from GenCC):

joint laxity, short stature, and myopia
Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae), G2P, Orphanet
Larsen syndrome
Inheritance: AR Classification: STRONG Submitted by: Genomics England PanelApp

GZF1 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=-0.75).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.329 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022482.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
GZF1	NM_022482.5	MANE Select	c.*1607C>A	3_prime_UTR	Exon 6 of 6	NP_071927.1
GZF1	NM_001317012.2		c.*1607C>A	3_prime_UTR	Exon 7 of 7	NP_001303941.1
GZF1	NM_001317019.1		c.*1663C>A	3_prime_UTR	Exon 5 of 5	NP_001303948.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GZF1	ENST00000338121.10	TSL:1 MANE Select	c.*1607C>A		3_prime_UTR	Exon 6 of 6	ENSP00000338290.5
	GZF1	ENST00000377051.2	TSL:1	c.*1607C>A		3_prime_UTR	Exon 5 of 5	ENSP00000366250.2

Frequencies

GnomAD3 genomes

AF:

0.290

AC:

43985

AN:

151902

Hom.:

6443

Cov.:

show subpopulations

Gnomad AFR

AF:

0.235

Gnomad AMI

AF:

0.401

Gnomad AMR

AF:

0.337

Gnomad ASJ

AF:

0.277

Gnomad EAS

AF:

0.331

Gnomad SAS

AF:

0.274

Gnomad FIN

AF:

0.296

Gnomad MID

AF:

0.373

Gnomad NFE

AF:

0.308

Gnomad OTH

AF:

0.294

GnomAD4 exome

AF:

0.265

AC:

115

AN:

434

Hom.:

Cov.:

AF XY:

0.256

AC XY:

AN XY:

262

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.265

AC:

113

AN:

426

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.500

AC:

AN:

Other (OTH)

AF:

0.167

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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

GnomAD4 genome

AF:

0.289

AC:

44002

AN:

152020

Hom.:

6446

Cov.:

AF XY:

0.292

AC XY:

21693

AN XY:

74298

show subpopulations

African (AFR)

AF:

0.234

AC:

9720

AN:

41474

American (AMR)

AF:

0.337

AC:

5147

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.277

AC:

961

AN:

3470

East Asian (EAS)

AF:

0.331

AC:

1710

AN:

5166

South Asian (SAS)

AF:

0.275

AC:

1329

AN:

4828

European-Finnish (FIN)

AF:

0.296

AC:

3124

AN:

10550

Middle Eastern (MID)

AF:

0.378

AC:

111

AN:

294

European-Non Finnish (NFE)

AF:

0.308

AC:

20917

AN:

67946

Other (OTH)

AF:

0.293

AC:

619

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1627

3254

4880

6507

8134

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

452

904

1356

1808

2260

<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:

0.305

Hom.:

27896

Bravo

AF:

0.293

Asia WGS

AF:

0.293

AC:

1019

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.75

CADD

Benign

7.2

(source)

DANN

Benign

0.62

PhyloP100

-0.17

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