Variant 11-46701135-G-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000311764.3(ZNF408):c.52+36G>C variant causes a intron 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. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0058 ( 9 hom., cov: 33)

Exomes 𝑓: 0.0030 ( 16 hom. )

Consequence

ZNF408
ENST00000311764.3 intron

Scores

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]

ZNF408 links:

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/exons	MANE	Protein	UniProt
ZNF408	NM_024741.3 linkuse as main transcript	c.52+36G>C		intron_variant		ENST00000311764.3	NP_079017.1
ZNF408	NM_001184751.2 linkuse as main transcript	c.22G>C	p.Gly8Arg	missense_variant	1/5		NP_001171680.1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris
ZNF408	ENST00000311764.3 linkuse as main transcript	c.52+36G>C	intron_variant	1	NM_024741.3	ENSP00000309606	P1
ZNF408	ENST00000526410.1 linkuse as main transcript	n.69+36G>C	intron_variant, non_coding_transcript_variant	3
ZNF408	ENST00000531866.1 linkuse as main transcript	n.70+36G>C	intron_variant, non_coding_transcript_variant	2

Frequencies

GnomAD3 genomes

AF:

0.00576

AC:

876

AN:

152170

Hom.:

Cov.:

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.:

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.:

Cov.:

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.:

Cov.:

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.:

Bravo

AF:

0.00574

Asia WGS

AF:

0.00144

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:4

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:3

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, no assertion criteria provided	clinical testing	Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	-	- -
Likely benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -

not specified

Benign:1

Benign, no assertion criteria provided

clinical testing

Clinical Genetics, Academic Medical Center

- -

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over