rs2395576

Positions:

• chr10-79424972-A-C
• chr10-79424972-A-G

Variant summary

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

The NM_153367.4(ZCCHC24):​c.447+7586T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.434 in 151,960 control chromosomes in the GnomAD database, including 16,025 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 (16025 hom., cov: 31)
• Consequence: ZCCHC24 NM_153367.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.875

Genes affected

ZCCHC24 (HGNC:26911): (zinc finger CCHC-type containing 24) Enables RNA 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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.674 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZCCHC24	NM_153367.4	c.447+7586T>G		intron_variant		ENST00000372336.4	NP_699198.2
ZCCHC24	XM_011539452.4	c.237+7586T>G		intron_variant			XP_011537754.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZCCHC24	ENST00000372336.4	c.447+7586T>G		intron_variant		1	NM_153367.4	ENSP00000361411.3
ZCCHC24	ENST00000372333.3	c.268+7586T>G		intron_variant		2		ENSP00000361408.3

Frequencies

GnomAD3 genomes AF: 0.434 AC: 65828 AN: 151842 Hom.: 15994 Cov.: 31

Gnomad AFR AF: 0.637

Gnomad AMI AF: 0.395

Gnomad AMR AF: 0.391

Gnomad ASJ AF: 0.261

Gnomad EAS AF: 0.692

Gnomad SAS AF: 0.338

Gnomad FIN AF: 0.373

Gnomad MID AF: 0.258

Gnomad NFE AF: 0.327

Gnomad OTH AF: 0.394

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

GnomAD4 genome AF: 0.434 AC: 65909 AN: 151960 Hom.: 16025 Cov.: 31 AF XY: 0.433 AC XY: 32158 AN XY: 74270

Gnomad4 AFR AF: 0.637

Gnomad4 AMR AF: 0.391

Gnomad4 ASJ AF: 0.261

Gnomad4 EAS AF: 0.693

Gnomad4 SAS AF: 0.338

Gnomad4 FIN AF: 0.373

Gnomad4 NFE AF: 0.327

Gnomad4 OTH AF: 0.390

Alfa AF: 0.363 Hom.: 3964

Bravo AF: 0.446

Asia WGS AF: 0.452 AC: 1573 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	4.2
DANN	Benign	0.84

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: rs2395576; hg19: chr10-81184728;