dbSNP rs8112177: ZNF888:c.142+1481C>T (chr19-52913715-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_001393938.1(ZNF888):c.142+1481C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.365 in 979,474 control chromosomes in the GnomAD database, including 67,172 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 0.43 ( 14746 hom., cov: 33)

Exomes 𝑓: 0.35 ( 52426 hom. )

Consequence

ZNF888
NM_001393938.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.973

Publications

2 publications found

Variant links:

Genes affected

ZNF888 (HGNC:38695): (zinc finger protein 888) 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]

ZNF888 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 (BayesDel_noAF=-1.04).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.533 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001393938.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ZNF888	NM_001393938.1	MANE Select	c.142+1481C>T	intron	N/A	NP_001380867.1	P0CJ79
ZNF888	NM_001384652.1		c.199+1481C>T	intron	N/A	NP_001371581.1
ZNF888	NM_001310127.2		c.142+1481C>T	intron	N/A	NP_001297056.1	P0CJ79

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ZNF888	ENST00000638862.2	TSL:5 MANE Select	c.142+1481C>T	intron	N/A	ENSP00000491567.1	P0CJ79
ZNF888	ENST00000884820.1		c.142+1481C>T	intron	N/A	ENSP00000554879.1
ZNF888	ENST00000933093.1		c.142+1481C>T	intron	N/A	ENSP00000603152.1

Frequencies

GnomAD3 genomes

AF:

0.429

AC:

65241

AN:

151916

Hom.:

14706

Cov.:

show subpopulations

Gnomad AFR

AF:

0.539

Gnomad AMI

AF:

0.407

Gnomad AMR

AF:

0.511

Gnomad ASJ

AF:

0.373

Gnomad EAS

AF:

0.412

Gnomad SAS

AF:

0.469

Gnomad FIN

AF:

0.420

Gnomad MID

AF:

0.269

Gnomad NFE

AF:

0.349

Gnomad OTH

AF:

0.402

GnomAD4 exome

AF:

0.353

AC:

292212

AN:

827440

Hom.:

52426

Cov.:

AF XY:

0.353

AC XY:

135057

AN XY:

382202

show subpopulations

African (AFR)

AF:

0.543

AC:

8393

AN:

15446

American (AMR)

AF:

0.571

AC:

555

AN:

972

Ashkenazi Jewish (ASJ)

AF:

0.373

AC:

1910

AN:

5116

East Asian (EAS)

AF:

0.404

AC:

1461

AN:

3612

South Asian (SAS)

AF:

0.467

AC:

7622

AN:

16312

European-Finnish (FIN)

AF:

0.430

AC:

116

AN:

270

Middle Eastern (MID)

AF:

0.255

AC:

411

AN:

1610

European-Non Finnish (NFE)

AF:

0.346

AC:

261749

AN:

756990

Other (OTH)

AF:

0.369

AC:

9995

AN:

27112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.446

Heterozygous variant carriers

8248

16497

24745

32994

41242

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

11664

23328

34992

46656

58320

<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:

0.430

AC:

65348

AN:

152034

Hom.:

14746

Cov.:

AF XY:

0.435

AC XY:

32293

AN XY:

74296

show subpopulations

African (AFR)

AF:

0.539

AC:

22337

AN:

41450

American (AMR)

AF:

0.512

AC:

7825

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.373

AC:

1296

AN:

3472

East Asian (EAS)

AF:

0.413

AC:

2136

AN:

5178

South Asian (SAS)

AF:

0.470

AC:

2268

AN:

4826

European-Finnish (FIN)

AF:

0.420

AC:

4434

AN:

10568

Middle Eastern (MID)

AF:

0.276

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.349

AC:

23735

AN:

67946

Other (OTH)

AF:

0.409

AC:

866

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1891

3782

5674

7565

9456

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

604

1208

1812

2416

3020

<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:

0.390

Hom.:

4000

Bravo

AF:

0.436

Asia WGS

AF:

0.508

AC:

1766

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

1.3

(source)

DANN

Benign

0.43

PhyloP100

-0.97

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over