dbSNP rs11208363: ZNF684:c.239-1780A>G (chr1-40544782-A-G) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_ModerateBA1

The NM_152373.4(ZNF684):c.239-1780A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.247 in 152,596 control chromosomes in the GnomAD database, including 5,941 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.25 ( 5930 hom., cov: 33)

Exomes 𝑓: 0.19 ( 11 hom. )

Consequence

ZNF684
NM_152373.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.17

Publications

10 publications found

Variant links:

Genes affected

ZNF684 (HGNC:28418): (zinc finger protein 684) Enables sequence-specific double-stranded DNA binding activity. Predicted to be involved in negative regulation of transcription by RNA polymerase II. Predicted to act upstream of or within innate immune response and negative regulation of single stranded viral RNA replication via double stranded DNA intermediate. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF684 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.41).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.524 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF684	NM_152373.4 link	c.239-1780A>G		intron_variant	Intron 4 of 4	ENST00000372699.8	NP_689586.3	Q5T5D7B3KSP5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF684	ENST00000372699.8 link	c.239-1780A>G		intron_variant	Intron 4 of 4	1	NM_152373.4	ENSP00000361784.3		Q5T5D7

Frequencies

GnomAD3 genomes

AF:

0.247

AC:

37530

AN:

152068

Hom.:

5920

Cov.:

show subpopulations

Gnomad AFR

AF:

0.376

Gnomad AMI

AF:

0.288

Gnomad AMR

AF:

0.342

Gnomad ASJ

AF:

0.154

Gnomad EAS

AF:

0.541

Gnomad SAS

AF:

0.353

Gnomad FIN

AF:

0.144

Gnomad MID

AF:

0.133

Gnomad NFE

AF:

0.139

Gnomad OTH

AF:

0.223

GnomAD4 exome

AF:

0.193

AC:

AN:

410

Hom.:

Cov.:

AF XY:

0.202

AC XY:

AN XY:

228

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AF:

0.396

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AF:

1.00

AC:

AN:

South Asian (SAS)

AF:

0.210

AC:

AN:

European-Finnish (FIN)

AF:

0.143

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.155

AC:

AN:

258

Other (OTH)

AF:

0.150

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

0.247

AC:

37600

AN:

152186

Hom.:

5930

Cov.:

AF XY:

0.250

AC XY:

18594

AN XY:

74408

show subpopulations

African (AFR)

AF:

0.376

AC:

15590

AN:

41476

American (AMR)

AF:

0.343

AC:

5241

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.154

AC:

536

AN:

3470

East Asian (EAS)

AF:

0.541

AC:

2802

AN:

5184

South Asian (SAS)

AF:

0.352

AC:

1695

AN:

4820

European-Finnish (FIN)

AF:

0.144

AC:

1530

AN:

10606

Middle Eastern (MID)

AF:

0.139

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.139

AC:

9428

AN:

68020

Other (OTH)

AF:

0.224

AC:

474

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1341

2682

4023

5364

6705

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

366

732

1098

1464

1830

<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:

0.179

Hom.:

13875

Bravo

AF:

0.269

Asia WGS

AF:

0.456

AC:

1586

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.41

CADD

Benign

(source)

DANN

Benign

0.89

PhyloP100

1.2

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

Computational scores

Splicing

Publications

Other links and lift over