dbSNP rs140900046: FIZ1:c.-1844C>T (chr19-55599709-G-A) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The ENST00000590714.1(FIZ1):c.-1844C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00842 in 152,536 control chromosomes in the GnomAD database, including 10 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 0.0084 ( 10 hom., cov: 32)

Exomes 𝑓: 0.0082 ( 0 hom. )

Consequence

FIZ1
ENST00000590714.1 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.18

Publications

6 publications found

Variant links:

Genes affected

FIZ1 (HGNC:25917): (FLT3 interacting zinc finger 1) This gene encodes zinc finger protein, which interacts with a receptor tyrosine kinase involved in the regulation of hematopoietic and lymphoid cells. This gene product also interacts with a transcription factor that regulates the expression of rod-specific genes in retina. [provided by RefSeq, Jul 2008]

FIZ1 links:

ZNF524 (HGNC:28322): (zinc finger protein 524) Enables sequence-specific double-stranded DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF524 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.59).

BS2

High AC in GnomAd4 at 1282 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
ZNF524	XM_011526487.3 link	c.-93G>A	5_prime_UTR_variant	Exon 1 of 2		XP_011524789.1
FIZ1	NM_032836.3 link	c.-272C>T	upstream_gene_variant		ENST00000221665.5	NP_116225.2
FIZ1	XM_005259352.5 link	c.-1251C>T	upstream_gene_variant			XP_005259409.1	Q96SL8
FIZ1	XM_047439564.1 link	c.-1844C>T	upstream_gene_variant			XP_047295520.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
FIZ1	ENST00000590714.1 link	c.-1844C>T	5_prime_UTR_variant	Exon 1 of 2	1		ENSP00000465131.1	K7EJE2
FIZ1	ENST00000221665.5 link	c.-272C>T	upstream_gene_variant		1	NM_032836.3	ENSP00000221665.2	Q96SL8
FIZ1	ENST00000592585.1 link	c.-272C>T	upstream_gene_variant		5		ENSP00000468529.1	K7ES33

Frequencies

GnomAD3 genomes

AF:

0.00842

AC:

1282

AN:

152174

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00246

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0101

Gnomad ASJ

AF:

0.00548

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000565

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0141

Gnomad OTH

AF:

0.0201

GnomAD4 exome

AF:

0.00820

AC:

AN:

244

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

178

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AF:

0.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AF:

0.00

AC:

AN:

European-Finnish (FIN)

AF:

0.0143

AC:

AN:

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00862

AC:

AN:

116

Other (OTH)

AF:

0.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

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:

0.00842

AC:

1282

AN:

152292

Hom.:

Cov.:

AF XY:

0.00736

AC XY:

548

AN XY:

74464

show subpopulations

African (AFR)

AF:

0.00245

AC:

102

AN:

41554

American (AMR)

AF:

0.0101

AC:

154

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.00548

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5172

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.000565

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0141

AC:

957

AN:

68022

Other (OTH)

AF:

0.0199

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

137

206

274

343

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00990

Hom.:

Bravo

AF:

0.00903

Asia WGS

AF:

0.00144

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.59

CADD

Benign

4.4

(source)

DANN

Benign

0.94

PhyloP100

1.2

PromoterAI

0.053

Neutral

(source)

Splicing

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over