Genetic Variant ZNF483:c.722-2352C>T (chr9-111539305-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_133464.5(ZNF483):c.722-2352C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.587 in 348,348 control chromosomes in the GnomAD database, including 61,437 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 0.59 ( 26502 hom., cov: 31)

Exomes 𝑓: 0.59 ( 34935 hom. )

Consequence

ZNF483
NM_133464.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.00600

Publications

19 publications found

Variant links:

Genes affected

ZNF483 (HGNC:23384): (zinc finger protein 483) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF483 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=-0.96).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.645 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_133464.5. 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
	ZNF483	NM_133464.5	MANE Select	c.722-2352C>T		intron	N/A	NP_597721.2
	ZNF483	NM_001007169.6		c.721+4952C>T		intron	N/A	NP_001007170.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
ZNF483	ENST00000309235.6	TSL:1 MANE Select	c.722-2352C>T	intron	N/A	ENSP00000311679.5
ZNF483	ENST00000355824.7	TSL:1	c.722-141C>T	intron	N/A	ENSP00000438048.1
ZNF483	ENST00000904413.1		c.722-2352C>T	intron	N/A	ENSP00000574477.1

Frequencies

GnomAD3 genomes

AF:

0.585

AC:

88851

AN:

151858

Hom.:

26488

Cov.:

show subpopulations

Gnomad AFR

AF:

0.540

Gnomad AMI

AF:

0.526

Gnomad AMR

AF:

0.475

Gnomad ASJ

AF:

0.599

Gnomad EAS

AF:

0.413

Gnomad SAS

AF:

0.515

Gnomad FIN

AF:

0.627

Gnomad MID

AF:

0.468

Gnomad NFE

AF:

0.650

Gnomad OTH

AF:

0.569

GnomAD4 exome

AF:

0.588

AC:

115478

AN:

196372

Hom.:

34935

AF XY:

0.582

AC XY:

64285

AN XY:

110430

show subpopulations

African (AFR)

AF:

0.516

AC:

2572

AN:

4986

American (AMR)

AF:

0.413

AC:

5580

AN:

13512

Ashkenazi Jewish (ASJ)

AF:

0.587

AC:

2871

AN:

4894

East Asian (EAS)

AF:

0.394

AC:

2883

AN:

7308

South Asian (SAS)

AF:

0.525

AC:

20754

AN:

39500

European-Finnish (FIN)

AF:

0.646

AC:

5553

AN:

8592

Middle Eastern (MID)

AF:

0.520

AC:

1022

AN:

1964

European-Non Finnish (NFE)

AF:

0.647

AC:

68756

AN:

106248

Other (OTH)

AF:

0.586

AC:

5487

AN:

9368

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

2155

4310

6464

8619

10774

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

362

724

1086

1448

1810

<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:

0.585

AC:

88909

AN:

151976

Hom.:

26502

Cov.:

AF XY:

0.577

AC XY:

42889

AN XY:

74300

show subpopulations

African (AFR)

AF:

0.540

AC:

22364

AN:

41444

American (AMR)

AF:

0.475

AC:

7244

AN:

15250

Ashkenazi Jewish (ASJ)

AF:

0.599

AC:

2078

AN:

3470

East Asian (EAS)

AF:

0.413

AC:

2139

AN:

5178

South Asian (SAS)

AF:

0.514

AC:

2476

AN:

4818

European-Finnish (FIN)

AF:

0.627

AC:

6606

AN:

10534

Middle Eastern (MID)

AF:

0.452

AC:

133

AN:

294

European-Non Finnish (NFE)

AF:

0.650

AC:

44200

AN:

67968

Other (OTH)

AF:

0.564

AC:

1190

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1914

3828

5741

7655

9569

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

752

1504

2256

3008

3760

<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:

0.625

Hom.:

106710

Bravo

AF:

0.572

Asia WGS

AF:

0.480

AC:

1670

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.96

CADD

Benign

8.2

(source)

DANN

Benign

0.37

PhyloP100

0.0060

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