dbSNP rs12982980: ZNF468:c.142+2490G>A (chr19-52846597-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001008801.2(ZNF468):c.142+2490G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.312 in 156,010 control chromosomes in the GnomAD database, including 9,994 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 0.32 ( 9994 hom., cov: 33)

Exomes 𝑓: 0.016 ( 0 hom. )

Consequence

ZNF468
NM_001008801.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.624

Publications

6 publications found

Variant links:

Genes affected

ZNF468 (HGNC:33105): (zinc finger protein 468) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF468 links:

ZNF28 (HGNC:13073): (zinc finger protein 28) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF28 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.8554392E-5).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.461 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF468	NM_001008801.2 link	c.142+2490G>A		intron_variant	Intron 3 of 3	ENST00000595646.6	NP_001008801.1	Q5VIY5-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF468	ENST00000595646.6 link	c.142+2490G>A		intron_variant	Intron 3 of 3	1	NM_001008801.2	ENSP00000470381.1		Q5VIY5-1

Frequencies

GnomAD3 genomes

AF:

0.320

AC:

48657

AN:

152008

Hom.:

9999

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0911

Gnomad AMI

AF:

0.341

Gnomad AMR

AF:

0.305

Gnomad ASJ

AF:

0.446

Gnomad EAS

AF:

0.0487

Gnomad SAS

AF:

0.216

Gnomad FIN

AF:

0.438

Gnomad MID

AF:

0.411

Gnomad NFE

AF:

0.465

Gnomad OTH

AF:

0.333

GnomAD2 exomes

AF:

0.591

AC:

AN:

AF XY:

0.750

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad FIN exome

AF:

0.500

Gnomad NFE exome

AF:

0.667

GnomAD4 exome

AF:

0.0157

AC:

AN:

3888

Hom.:

Cov.:

AF XY:

0.0164

AC XY:

AN XY:

1890

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00420

AC:

AN:

238

American (AMR)

AF:

0.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AF:

0.0141

AC:

AN:

142

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0171

AC:

AN:

3278

Other (OTH)

AF:

0.0132

AC:

AN:

152

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.297

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.320

AC:

48637

AN:

152122

Hom.:

9994

Cov.:

AF XY:

0.315

AC XY:

23388

AN XY:

74350

show subpopulations

African (AFR)

AF:

0.0909

AC:

3774

AN:

41518

American (AMR)

AF:

0.305

AC:

4654

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.446

AC:

1546

AN:

3468

East Asian (EAS)

AF:

0.0484

AC:

251

AN:

5188

South Asian (SAS)

AF:

0.215

AC:

1035

AN:

4818

European-Finnish (FIN)

AF:

0.438

AC:

4628

AN:

10564

Middle Eastern (MID)

AF:

0.418

AC:

123

AN:

294

European-Non Finnish (NFE)

AF:

0.465

AC:

31622

AN:

67978

Other (OTH)

AF:

0.329

AC:

694

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1524

3048

4571

6095

7619

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.375

Hom.:

10145

Bravo

AF:

0.299

TwinsUK

AF:

0.467

AC:

1730

ALSPAC

AF:

0.459

AC:

1770

ExAC

AF:

0.148

AC:

485

Asia WGS

AF:

0.119

AC:

416

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.52

CADD

Benign

7.3

(source)

DANN

Benign

0.41

FATHMM_MKL

Benign

0.017

LIST_S2

Benign

0.27

MetaRNN

Benign

0.000019

PhyloP100

0.62

GERP RS

0.39

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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rs12982980

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