rs7625204

chr3-102340043-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000491959.5(ZPLD1):c.-508-43747C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.148 in 152,020 control chromosomes in the GnomAD database, including 2,100 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 0.15 (2100 hom., cov: 32)
• Consequence: ZPLD1 ENST00000491959.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.833

Genes affected

ZPLD1 (HGNC:27022): (zona pellucida like domain containing 1) Predicted to be an extracellular matrix structural constituent. Predicted to act upstream of or within vestibular reflex. Predicted to be located in cytoplasmic vesicle membrane. Predicted to be integral component of membrane. Predicted to be active in cell surface and extracellular space. [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=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.206 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZPLD1	ENST00000491959.5	c.-508-43747C>T		intron_variant		1		P1

Frequencies

GnomAD3 genomes AF: 0.148 AC: 22545 AN: 151902 Hom.: 2098 Cov.: 32

Gnomad AFR AF: 0.0591

Gnomad AMI AF: 0.158

Gnomad AMR AF: 0.149

Gnomad ASJ AF: 0.250

Gnomad EAS AF: 0.0115

Gnomad SAS AF: 0.148

Gnomad FIN AF: 0.141

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.208

Gnomad OTH AF: 0.157

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.148 AC: 22547 AN: 152020 Hom.: 2100 Cov.: 32 AF XY: 0.144 AC XY: 10717 AN XY: 74294

Gnomad4 AFR AF: 0.0592

Gnomad4 AMR AF: 0.148

Gnomad4 ASJ AF: 0.250

Gnomad4 EAS AF: 0.0115

Gnomad4 SAS AF: 0.147

Gnomad4 FIN AF: 0.141

Gnomad4 NFE AF: 0.209

Gnomad4 OTH AF: 0.155

Alfa AF: 0.200 Hom.: 6386

Bravo AF: 0.145

Asia WGS AF: 0.0770 AC: 272 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	6.7
Dann	Benign	0.59

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

Other links and lift over

dbSNP: rs7625204; hg19: chr3-102058887;