rs148055528

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 2P and 16B. PM4BP6_Very_StrongBA1

The NM_024741.3(ZNF408):c.581_592delTGACAGAAGTGG(p.Val194_Val197del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.159 in 1,611,622 control chromosomes in the GnomAD database, including 27,861 homozygotes. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.14 ( 2434 hom., cov: 30)

Exomes 𝑓: 0.16 ( 25427 hom. )

Consequence

ZNF408
NM_024741.3 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts U:1B:4

Conservation

PhyloP100: 3.10

Publications

12 publications found

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 Gene-Disease associations (from GenCC):

exudative vitreoretinopathy 6
Inheritance: AD Classification: STRONG, LIMITED Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
retinitis pigmentosa 72
Inheritance: AR Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
exudative vitreoretinopathy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
retinitis pigmentosa
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ZNF408 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

PM4

Nonframeshift variant in NON repetitive region in NM_024741.3.

BP6

Variant 11-46703166-CAGTGGTGACAGA-C is Benign according to our data. Variant chr11-46703166-CAGTGGTGACAGA-C is described in ClinVar as Benign. ClinVar VariationId is 261760.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.565 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF408	NM_024741.3 link	c.581_592delTGACAGAAGTGG	p.Val194_Val197del	disruptive_inframe_deletion	Exon 4 of 5	ENST00000311764.3	NP_079017.1
ZNF408	NM_001184751.2 link	c.557_568delTGACAGAAGTGG	p.Val186_Val189del	disruptive_inframe_deletion	Exon 4 of 5		NP_001171680.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF408	ENST00000311764.3 link	c.581_592delTGACAGAAGTGG	p.Val194_Val197del	disruptive_inframe_deletion	Exon 4 of 5	1	NM_024741.3	ENSP00000309606.2
ZNF408	ENST00000527008.1 link	n.458_469delTGACAGAAGTGG		non_coding_transcript_exon_variant	Exon 1 of 2	2

Frequencies

GnomAD3 genomes

AF:

0.141

AC:

21439

AN:

152094

Hom.:

2422

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0309

Gnomad AMI

AF:

0.0811

Gnomad AMR

AF:

0.235

Gnomad ASJ

AF:

0.0799

Gnomad EAS

AF:

0.582

Gnomad SAS

AF:

0.211

Gnomad FIN

AF:

0.250

Gnomad MID

AF:

0.120

Gnomad NFE

AF:

0.136

Gnomad OTH

AF:

0.125

GnomAD2 exomes

AF:

0.200

AC:

48794

AN:

243712

AF XY:

0.193

show subpopulations

Gnomad AFR exome

AF:

0.0262

Gnomad AMR exome

AF:

0.382

Gnomad ASJ exome

AF:

0.0741

Gnomad EAS exome

AF:

0.584

Gnomad FIN exome

AF:

0.230

Gnomad NFE exome

AF:

0.120

Gnomad OTH exome

AF:

0.148

GnomAD4 exome

AF:

0.160

AC:

234119

AN:

1459410

Hom.:

25427

AF XY:

0.161

AC XY:

116558

AN XY:

725970

show subpopulations

African (AFR)

AF:

0.0225

AC:

752

AN:

33466

American (AMR)

AF:

0.370

AC:

16280

AN:

44000

Ashkenazi Jewish (ASJ)

AF:

0.0762

AC:

1989

AN:

26090

East Asian (EAS)

AF:

0.603

AC:

23788

AN:

39460

South Asian (SAS)

AF:

0.209

AC:

17968

AN:

86002

European-Finnish (FIN)

AF:

0.228

AC:

12134

AN:

53136

Middle Eastern (MID)

AF:

0.111

AC:

641

AN:

5756

European-Non Finnish (NFE)

AF:

0.136

AC:

151322

AN:

1111198

Other (OTH)

AF:

0.153

AC:

9245

AN:

60302

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.456

Heterozygous variant carriers

10883

21766

32650

43533

54416

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5806

11612

17418

23224

29030

<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:

0.141

AC:

21454

AN:

152212

Hom.:

2434

Cov.:

AF XY:

0.151

AC XY:

11216

AN XY:

74396

show subpopulations

African (AFR)

AF:

0.0308

AC:

1281

AN:

41574

American (AMR)

AF:

0.236

AC:

3603

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.0799

AC:

277

AN:

3468

East Asian (EAS)

AF:

0.583

AC:

2997

AN:

5144

South Asian (SAS)

AF:

0.212

AC:

1022

AN:

4830

European-Finnish (FIN)

AF:

0.250

AC:

2654

AN:

10606

Middle Eastern (MID)

AF:

0.112

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.136

AC:

9255

AN:

67994

Other (OTH)

AF:

0.122

AC:

258

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

786

1572

2358

3144

3930

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

242

484

726

968

1210

<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:

0.128

Hom.:

245

Bravo

AF:

0.139

Asia WGS

AF:

0.310

AC:

1075

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Uncertain:1Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Retinal dystrophy

Uncertain:1Benign:1

Oct 01, 2023

Dept Of Ophthalmology, Nagoya University

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:research

- -

Jan 01, 2022

Institute of Human Genetics, Univ. Regensburg, Univ. Regensburg

Significance:Uncertain significance

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

not provided

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

May 05, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

3.1

Mutation Taster

=185/15

polymorphism (auto)

(source)

Splicing

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over