rs17768650

Positions:

• chr10-45651632-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

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

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]

ACMG classification

Verdict is Benign. Variant got -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 male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 97 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZFAND4	NM_174890.4	c.328+334C>G		intron_variant		ENST00000344646.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZFAND4	ENST00000344646.10	c.328+334C>G		intron_variant		1	NM_174890.4	P1

Frequencies

GnomAD3 genomes AF: 0.0337 AC: 5123 AN: 152106 Hom.: 94 Cov.: 32

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

GnomAD3 exomes AF: 0.0299 AC: 4457 AN: 148998 Hom.: 86 AF XY: 0.0300 AC XY: 2410 AN XY: 80276

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 SAS exome AF: 0.0229

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.: 0 AF XY: 0.0302 AC XY: 5591 AN XY: 185028

Gnomad4 AFR exome AF: 0.0366

Gnomad4 AMR exome AF: 0.0197

Gnomad4 ASJ exome AF: 0.0179

Gnomad4 EAS exome AF: 0.0484

Gnomad4 SAS exome AF: 0.0216

Gnomad4 FIN exome AF: 0.0416

Gnomad4 NFE exome AF: 0.0346

Gnomad4 OTH exome AF: 0.0331

GnomAD4 genome AF: 0.0337 AC: 5132 AN: 152224 Hom.: 97 Cov.: 32 AF XY: 0.0338 AC XY: 2513 AN XY: 74440

Gnomad4 AFR AF: 0.0345

Gnomad4 AMR AF: 0.0286

Gnomad4 ASJ AF: 0.0164

Gnomad4 EAS AF: 0.0524

Gnomad4 SAS AF: 0.0195

Gnomad4 FIN AF: 0.0371

Gnomad4 NFE AF: 0.0346

Gnomad4 OTH AF: 0.0293

Alfa AF: 0.0321 Hom.: 31

Bravo AF: 0.0332

Asia WGS AF: 0.0360 AC: 124 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.87
DANN	Benign	0.40

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

LitVar

Other links and lift over

dbSNP: rs17768650; hg19: chr10-46147080;