Genetic Variant NM_152373.4:c.239-1780A>G (chr1-40544782-A-G) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. Variant got -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

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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

Gnomad4 AMR exome

AF:

0.396

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

1.00

Gnomad4 SAS exome

AF:

0.210

Gnomad4 FIN exome

AF:

0.143

Gnomad4 NFE exome

AF:

0.155

Gnomad4 OTH exome

AF:

0.150

GnomAD4 genome

AF:

0.247

AC:

37600

AN:

152186

Hom.:

5930

Cov.:

AF XY:

0.250

AC XY:

18594

AN XY:

74408

show subpopulations

Gnomad4 AFR

AF:

0.376

Gnomad4 AMR

AF:

0.343

Gnomad4 ASJ

AF:

0.154

Gnomad4 EAS

AF:

0.541

Gnomad4 SAS

AF:

0.352

Gnomad4 FIN

AF:

0.144

Gnomad4 NFE

AF:

0.139

Gnomad4 OTH

AF:

0.224

Alfa

AF:

0.167

Hom.:

5636

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

DANN

Benign

0.89

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

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over