Variant chr5-124639221-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_ModerateBP6_ModerateBS1BS2

The NM_020747.3(ZNF608):c.4451-7C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00684 in 1,613,696 control chromosomes in the GnomAD database, including 76 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0055 ( 7 hom., cov: 33)

Exomes 𝑓: 0.0070 ( 69 hom. )

Consequence

ZNF608
NM_020747.3 splice_region, intron

Scores

Splicing: ADA: 0.004369

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.17

Variant links:

Genes affected

ZNF608 (HGNC:29238): (zinc finger protein 608) Predicted to enable metal ion binding activity. Predicted to be involved in negative regulation of transcription by RNA polymerase II. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF608 links:

ZNF608 (HGNC:):

ZNF608 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.38).

BP6

Variant 5-124639221-G-A is Benign according to our data. Variant chr5-124639221-G-A is described in ClinVar as [Benign]. Clinvar id is 773323.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00551 (839/152328) while in subpopulation SAS AF= 0.0193 (93/4828). AF 95% confidence interval is 0.0161. There are 7 homozygotes in gnomad4. There are 412 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 839 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF608	NM_020747.3 linkuse as main transcript	c.4451-7C>T		splice_region_variant, intron_variant		ENST00000513986.2	NP_065798.2	Q9ULD9-1B3KPE6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF608	ENST00000513986.2 linkuse as main transcript	c.4451-7C>T		splice_region_variant, intron_variant		2	NM_020747.3	ENSP00000421899.2		Q9ULD9-1B3KPE6

Frequencies

GnomAD3 genomes

AF:

0.00550

AC:

837

AN:

152210

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00113

Gnomad AMI

AF:

0.0789

Gnomad AMR

AF:

0.00504

Gnomad ASJ

AF:

0.00749

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.0188

Gnomad FIN

AF:

0.00113

Gnomad MID

AF:

0.0191

Gnomad NFE

AF:

0.00714

Gnomad OTH

AF:

0.00909

GnomAD3 exomes

AF:

0.00690

AC:

1734

AN:

251182

Hom.:

AF XY:

0.00802

AC XY:

1089

AN XY:

135788

show subpopulations

Gnomad AFR exome

AF:

0.000863

Gnomad AMR exome

AF:

0.00405

Gnomad ASJ exome

AF:

0.00874

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.0192

Gnomad FIN exome

AF:

0.000971

Gnomad NFE exome

AF:

0.00736

Gnomad OTH exome

AF:

0.00752

GnomAD4 exome

AF:

0.00697

AC:

10192

AN:

1461368

Hom.:

Cov.:

AF XY:

0.00750

AC XY:

5455

AN XY:

726986

show subpopulations

Gnomad4 AFR exome

AF:

0.00111

Gnomad4 AMR exome

AF:

0.00463

Gnomad4 ASJ exome

AF:

0.00742

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0197

Gnomad4 FIN exome

AF:

0.00112

Gnomad4 NFE exome

AF:

0.00672

Gnomad4 OTH exome

AF:

0.00658

GnomAD4 genome

AF:

0.00551

AC:

839

AN:

152328

Hom.:

Cov.:

AF XY:

0.00553

AC XY:

412

AN XY:

74484

show subpopulations

Gnomad4 AFR

AF:

0.00113

Gnomad4 AMR

AF:

0.00503

Gnomad4 ASJ

AF:

0.00749

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.0193

Gnomad4 FIN

AF:

0.00113

Gnomad4 NFE

AF:

0.00716

Gnomad4 OTH

AF:

0.00900

Alfa

AF:

0.00669

Hom.:

Bravo

AF:

0.00593

Asia WGS

AF:

0.00606

AC:

AN:

3478

EpiCase

AF:

0.00932

EpiControl

AF:

0.00854

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jul 05, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.38

CADD

Benign

DANN

Benign

0.90

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0044

dbscSNV1_RF

Benign

0.080

SpliceAI score (max)

0.030

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