dbSNP rs17768650: ZFAND4:c.328+334C>G (chr10-45651632-G-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_174890.4(ZFAND4):c.328+334C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.032 in 480,870 control chromosomes in the GnomAD database, including 296 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 0.034 ( 97 hom., cov: 32)

Exomes 𝑓: 0.031 ( 199 hom. )

Consequence

ZFAND4
NM_174890.4 intron

Scores

Splicing: ADA: 0.00001992

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.218

Publications

3 publications found

Variant links:

Genes affected

ZFAND4 (HGNC:23504): (zinc finger AN1-type containing 4) Predicted to enable zinc ion binding activity. [provided by Alliance of Genome Resources, Apr 2022]

ZFAND4 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=-0.89).

BS1

Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.0337 (5132/152224) while in subpopulation EAS AF = 0.0524 (271/5174). AF 95% confidence interval is 0.0473. There are 97 homozygotes in GnomAd4. There are 2513 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 97 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_174890.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ZFAND4	NM_174890.4	MANE Select	c.328+334C>G	intron	N/A	NP_777550.2	Q86XD8
ZFAND4	NM_001128324.2		c.328+334C>G	intron	N/A	NP_001121796.1	Q86XD8
ZFAND4	NM_001282905.1		c.106+334C>G	intron	N/A	NP_001269834.1	J3KPC0

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ZFAND4	ENST00000344646.10	TSL:1 MANE Select	c.328+334C>G	intron	N/A	ENSP00000339484.5	Q86XD8
ZFAND4	ENST00000374366.7	TSL:1	c.106+334C>G	intron	N/A	ENSP00000363486.3	J3KPC0
ZFAND4	ENST00000947494.1		c.328+334C>G	intron	N/A	ENSP00000617553.1

Frequencies

GnomAD3 genomes

AF:

0.0337

AC:

5123

AN:

152106

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0343

Gnomad AMI

AF:

0.0230

Gnomad AMR

AF:

0.0286

Gnomad ASJ

AF:

0.0164

Gnomad EAS

AF:

0.0524

Gnomad SAS

AF:

0.0197

Gnomad FIN

AF:

0.0371

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.0347

Gnomad OTH

AF:

0.0296

GnomAD2 exomes

AF:

0.0299

AC:

4457

AN:

148998

AF XY:

0.0300

show subpopulations

Gnomad AFR exome

AF:

0.0357

Gnomad AMR exome

AF:

0.0208

Gnomad ASJ exome

AF:

0.0177

Gnomad EAS exome

AF:

0.0401

Gnomad FIN exome

AF:

0.0416

Gnomad NFE exome

AF:

0.0327

Gnomad OTH exome

AF:

0.0262

GnomAD4 exome

AF:

0.0313

AC:

10275

AN:

328646

Hom.:

199

Cov.:

AF XY:

0.0302

AC XY:

5591

AN XY:

185028

show subpopulations

African (AFR)

AF:

0.0366

AC:

333

AN:

9106

American (AMR)

AF:

0.0197

AC:

544

AN:

27582

Ashkenazi Jewish (ASJ)

AF:

0.0179

AC:

203

AN:

11312

East Asian (EAS)

AF:

0.0484

AC:

483

AN:

9970

South Asian (SAS)

AF:

0.0216

AC:

1293

AN:

59794

European-Finnish (FIN)

AF:

0.0416

AC:

1137

AN:

27364

Middle Eastern (MID)

AF:

0.0203

AC:

AN:

2852

European-Non Finnish (NFE)

AF:

0.0346

AC:

5726

AN:

165628

Other (OTH)

AF:

0.0331

AC:

498

AN:

15038

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.459

Heterozygous variant carriers

472

944

1417

1889

2361

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

108

144

180

<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:

0.0337

AC:

5132

AN:

152224

Hom.:

Cov.:

AF XY:

0.0338

AC XY:

2513

AN XY:

74440

show subpopulations

African (AFR)

AF:

0.0345

AC:

1434

AN:

41530

American (AMR)

AF:

0.0286

AC:

437

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.0164

AC:

AN:

3470

East Asian (EAS)

AF:

0.0524

AC:

271

AN:

5174

South Asian (SAS)

AF:

0.0195

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.0371

AC:

393

AN:

10604

Middle Eastern (MID)

AF:

0.0238

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0346

AC:

2356

AN:

68016

Other (OTH)

AF:

0.0293

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

258

517

775

1034

1292

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

180

240

300

<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:

0.0321

Hom.:

Bravo

AF:

0.0332

Asia WGS

AF:

0.0360

AC:

124

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.87

(source)

DANN

Benign

0.40

PhyloP100

-0.22

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000020

dbscSNV1_RF

Benign

0.0

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