11-46701135-G-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_001184751.2(ZNF408):ā€‹c.22G>Cā€‹(p.Gly8Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0033 in 1,613,928 control chromosomes in the GnomAD database, including 25 homozygotes. In-silico tool predicts a benign outcome for this variant. 5/5 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā˜…).

Frequency

Genomes: š‘“ 0.0058 ( 9 hom., cov: 33)
Exomes š‘“: 0.0030 ( 16 hom. )

Consequence

ZNF408
NM_001184751.2 missense

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:4

Conservation

PhyloP100: 0.160
Variant links:
Genes affected
ZNF408 (HGNC:20041): (zinc finger protein 408) The protein encoded by this gene contains ten tandem zinc fingers and an N-terminal SET domain, so it is likely a DNA binding protein that interacts with other proteins. In adults, the encoded protein is expressed most highly in retina. Consequently, defects in this gene have been associated with familial exudative vitreoretinopathy (FEVR) and retinitis pigmentosa (RP). [provided by RefSeq, Dec 2016]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.81).
BP6
Variant 11-46701135-G-C is Benign according to our data. Variant chr11-46701135-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 1206255.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-46701135-G-C is described in Lovd as [Benign]. Variant chr11-46701135-G-C is described in Lovd as [Likely_benign].
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00577 (878/152288) while in subpopulation AFR AF= 0.0135 (560/41554). AF 95% confidence interval is 0.0126. There are 9 homozygotes in gnomad4. There are 419 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 9 AD,AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ZNF408NM_024741.3 linkc.52+36G>C intron_variant Intron 1 of 4 ENST00000311764.3 NP_079017.1 Q9H9D4
ZNF408NM_001184751.2 linkc.22G>C p.Gly8Arg missense_variant Exon 1 of 5 NP_001171680.1 Q9H9D4B4DXY4

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ZNF408ENST00000311764.3 linkc.52+36G>C intron_variant Intron 1 of 4 1 NM_024741.3 ENSP00000309606.2 Q9H9D4
ZNF408ENST00000526410.1 linkn.69+36G>C intron_variant Intron 1 of 2 3
ZNF408ENST00000531866.1 linkn.70+36G>C intron_variant Intron 1 of 1 2

Frequencies

GnomAD3 genomes
AF:
0.00576
AC:
876
AN:
152170
Hom.:
9
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0135
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00164
Gnomad ASJ
AF:
0.0179
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00358
Gnomad MID
AF:
0.00633
Gnomad NFE
AF:
0.00266
Gnomad OTH
AF:
0.00383
GnomAD3 exomes
AF:
0.00333
AC:
830
AN:
248886
Hom.:
1
AF XY:
0.00324
AC XY:
437
AN XY:
134810
show subpopulations
Gnomad AFR exome
AF:
0.0136
Gnomad AMR exome
AF:
0.00231
Gnomad ASJ exome
AF:
0.0183
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000163
Gnomad FIN exome
AF:
0.00316
Gnomad NFE exome
AF:
0.00224
Gnomad OTH exome
AF:
0.00377
GnomAD4 exome
AF:
0.00304
AC:
4445
AN:
1461640
Hom.:
16
Cov.:
31
AF XY:
0.00300
AC XY:
2182
AN XY:
727124
show subpopulations
Gnomad4 AFR exome
AF:
0.0155
Gnomad4 AMR exome
AF:
0.00217
Gnomad4 ASJ exome
AF:
0.0171
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000174
Gnomad4 FIN exome
AF:
0.00225
Gnomad4 NFE exome
AF:
0.00264
Gnomad4 OTH exome
AF:
0.00460
GnomAD4 genome
AF:
0.00577
AC:
878
AN:
152288
Hom.:
9
Cov.:
33
AF XY:
0.00563
AC XY:
419
AN XY:
74476
show subpopulations
Gnomad4 AFR
AF:
0.0135
Gnomad4 AMR
AF:
0.00163
Gnomad4 ASJ
AF:
0.0179
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000414
Gnomad4 FIN
AF:
0.00358
Gnomad4 NFE
AF:
0.00266
Gnomad4 OTH
AF:
0.00379
Alfa
AF:
0.00332
Hom.:
4
Bravo
AF:
0.00574
Asia WGS
AF:
0.00144
AC:
5
AN:
3478

ClinVar

Significance: Likely benign
Submissions summary: Benign:4
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:3
-
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center
Significance: Likely benign
Review Status: no assertion criteria provided
Collection Method: clinical testing

- -

-
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)
Significance: Likely benign
Review Status: no assertion criteria provided
Collection Method: clinical testing

- -

-
Breakthrough Genomics, Breakthrough Genomics
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: not provided

- -

not specified Benign:1
-
Clinical Genetics, Academic Medical Center
Significance: Benign
Review Status: no assertion criteria provided
Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.81
CADD
Benign
5.1
DANN
Benign
0.52

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.050
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs111794632; hg19: chr11-46722685; API