Variant chr11-46702739-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_024741.3(ZNF408):c.366C>G(p.Ala122Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0164 in 1,614,084 control chromosomes in the GnomAD database, including 3,814 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.086 ( 1902 hom., cov: 33)

Exomes 𝑓: 0.0091 ( 1912 hom. )

Consequence

ZNF408
NM_024741.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.890

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:

ZNF408 (HGNC:):

ZNF408 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.68).

BP6

Variant 11-46702739-C-G is Benign according to our data. Variant chr11-46702739-C-G is described in ClinVar as [Benign]. Clinvar id is 261759.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.89 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.296 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF408	NM_024741.3 linkuse as main transcript	c.366C>G	p.Ala122Ala	synonymous_variant	3/5	ENST00000311764.3	NP_079017.1	Q9H9D4
ZNF408	NM_001184751.2 linkuse as main transcript	c.342C>G	p.Ala114Ala	synonymous_variant	3/5		NP_001171680.1	Q9H9D4B4DXY4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ZNF408	ENST00000311764.3 linkuse as main transcript	c.366C>G	p.Ala122Ala	synonymous_variant	3/5	1	NM_024741.3	ENSP00000309606.2	Q9H9D4
ZNF408	ENST00000526410.1 linkuse as main transcript	n.383C>G		non_coding_transcript_exon_variant	3/3	3
ZNF408	ENST00000527008.1 linkuse as main transcript	n.25C>G		non_coding_transcript_exon_variant	1/2	2
ZNF408	ENST00000534481.1 linkuse as main transcript	n.505C>G		non_coding_transcript_exon_variant	2/2	4

Frequencies

GnomAD3 genomes

AF:

0.0862

AC:

13111

AN:

152126

Hom.:

1893

Cov.:

show subpopulations

Gnomad AFR

AF:

0.301

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0297

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00227

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0443

Gnomad NFE

AF:

0.000823

Gnomad OTH

AF:

0.0666

GnomAD3 exomes

AF:

0.0222

AC:

5588

AN:

251482

Hom.:

797

AF XY:

0.0165

AC XY:

2245

AN XY:

135916

show subpopulations

Gnomad AFR exome

AF:

0.304

Gnomad AMR exome

AF:

0.0135

Gnomad ASJ exome

AF:

0.00109

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.000784

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000791

Gnomad OTH exome

AF:

0.00945

GnomAD4 exome

AF:

0.00915

AC:

13373

AN:

1461840

Hom.:

1912

Cov.:

AF XY:

0.00786

AC XY:

5719

AN XY:

727212

show subpopulations

Gnomad4 AFR exome

AF:

0.323

Gnomad4 AMR exome

AF:

0.0151

Gnomad4 ASJ exome

AF:

0.000995

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00107

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000403

Gnomad4 OTH exome

AF:

0.0203

GnomAD4 genome

AF:

0.0863

AC:

13145

AN:

152244

Hom.:

1902

Cov.:

AF XY:

0.0839

AC XY:

6244

AN XY:

74446

show subpopulations

Gnomad4 AFR

AF:

0.300

Gnomad4 AMR

AF:

0.0297

Gnomad4 ASJ

AF:

0.00144

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000823

Gnomad4 OTH

AF:

0.0659

Alfa

AF:

0.0250

Hom.:

170

Bravo

AF:

0.0973

Asia WGS

AF:

0.0210

AC:

AN:

3478

EpiCase

AF:

0.000818

EpiControl

AF:

0.000771

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 30, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 05, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	May 09, 2018	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.68

CADD

Benign

8.0

DANN

Benign

0.62

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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