Genetic Variant ZIC4:c.1005-15A>C (chr3-147388874-T-G) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_ModerateBP6_Moderate

The NM_032153.6(ZIC4):c.1005-15A>C variant causes a intron change. The variant allele was found at a frequency of 0.000283 in 779,746 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00093 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00013 ( 0 hom. )

Consequence

ZIC4
NM_032153.6 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 4.31

Publications

0 publications found

Variant links:

Genes affected

ZIC4 (HGNC:20393): (Zic family member 4) This gene encodes a member of the ZIC family of C2H2-type zinc finger proteins. Members of this family are important during development, and have been associated with X-linked visceral heterotaxy and holoprosencephaly type 5. This gene is closely linked to the gene encoding zinc finger protein of the cerebellum 1, a related family member on chromosome 3. Heterozygous deletion of these linked genes is involved in Dandy-Walker malformation, which is a congenital cerebellar malformation. Multiple transcript variants have been identified for this gene. [provided by RefSeq, Dec 2009]

ZIC4 links:

ZIC4-AS1 (HGNC:40920): (ZIC4 antisense RNA 1)

ZIC4-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.29).

BP6

Variant 3-147388874-T-G is Benign according to our data. Variant chr3-147388874-T-G is described in ClinVar as Benign. ClinVar VariationId is 2863667.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032153.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ZIC4	NM_032153.6	MANE Select	c.1005-15A>C	intron	N/A	NP_115529.2
ZIC4	NM_001168378.1		c.1155-15A>C	intron	N/A	NP_001161850.1	Q8N9L1-3
ZIC4	NM_001168379.2		c.1119-15A>C	intron	N/A	NP_001161851.1	Q8N9L1-5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ZIC4	ENST00000383075.8	TSL:1 MANE Select	c.1005-15A>C	intron	N/A	ENSP00000372553.3	Q8N9L1-1
ZIC4	ENST00000525172.6	TSL:2	c.1155-15A>C	intron	N/A	ENSP00000435509.2	Q8N9L1-3
ZIC4	ENST00000425731.7	TSL:2	c.1119-15A>C	intron	N/A	ENSP00000397695.3	Q8N9L1-5

Frequencies

GnomAD3 genomes

AF:

0.000934

AC:

142

AN:

152096

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00336

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000956

GnomAD2 exomes

AF:

0.000258

AC:

AN:

248372

AF XY:

0.000223

show subpopulations

Gnomad AFR exome

AF:

0.00401

Gnomad AMR exome

AF:

0.0000586

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000126

AC:

AN:

627532

Hom.:

Cov.:

AF XY:

0.000111

AC XY:

AN XY:

341858

show subpopulations

African (AFR)

AF:

0.00380

AC:

AN:

17630

American (AMR)

AF:

0.0000461

AC:

AN:

43348

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

20966

East Asian (EAS)

AF:

0.00

AC:

AN:

35980

South Asian (SAS)

AF:

0.0000144

AC:

AN:

69462

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53136

Middle Eastern (MID)

AF:

0.000242

AC:

AN:

4132

European-Non Finnish (NFE)

AF:

0.00000286

AC:

AN:

349822

Other (OTH)

AF:

0.000212

AC:

AN:

33056

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.464

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:

0.000933

AC:

142

AN:

152214

Hom.:

Cov.:

AF XY:

0.000846

AC XY:

AN XY:

74428

show subpopulations

African (AFR)

AF:

0.00335

AC:

139

AN:

41540

American (AMR)

AF:

0.0000653

AC:

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5162

South Asian (SAS)

AF:

0.00

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10596

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67998

Other (OTH)

AF:

0.000946

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.000477

Hom.:

Bravo

AF:

0.000990

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.29

CADD

Benign

(source)

DANN

Benign

0.86

PhyloP100

4.3

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

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over