rs13149511

Positions:

• chr4-25356487-G-A
• chr4-25356487-G-C
• chr4-25356487-G-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_024936.3(ZCCHC4):​c.1011+4798G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.907 in 152,046 control chromosomes in the GnomAD database, including 62,709 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 0.91 (62709 hom., cov: 30)
• Consequence: ZCCHC4 NM_024936.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.75

Genes affected

ZCCHC4 (HGNC:22917): (zinc finger CCHC-type containing 4) Enables S-adenosyl-L-methionine binding activity; rRNA (adenine-N6-)-methyltransferase activity; and zinc ion binding activity. Involved in positive regulation of translation and rRNA methylation. Located in cytoplasm and nucleolus. [provided by Alliance of Genome Resources, Apr 2022]

ZCCHC4 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.33).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.968 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZCCHC4	NM_024936.3	c.1011+4798G>A		intron_variant		ENST00000302874.9	NP_079212.2
ZCCHC4	XM_011513835.3	c.1056+3312G>A		intron_variant			XP_011512137.1
ZCCHC4	XM_017008129.3	c.760-5372G>A		intron_variant			XP_016863618.1
ZCCHC4	XR_925324.4	n.1092+3312G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZCCHC4	ENST00000302874.9	c.1011+4798G>A		intron_variant		1	NM_024936.3	ENSP00000303468.4
ZCCHC4	ENST00000507760.5	n.687-5372G>A		intron_variant		1		ENSP00000422115.1
ZCCHC4	ENST00000505412.1	c.603+4798G>A		intron_variant		3		ENSP00000422269.1

Frequencies

GnomAD3 genomes AF: 0.906 AC: 137720 AN: 151928 Hom.: 62647 Cov.: 30

Gnomad AFR AF: 0.976

Gnomad AMI AF: 0.881

Gnomad AMR AF: 0.869

Gnomad ASJ AF: 0.852

Gnomad EAS AF: 0.763

Gnomad SAS AF: 0.828

Gnomad FIN AF: 0.920

Gnomad MID AF: 0.883

Gnomad NFE AF: 0.890

Gnomad OTH AF: 0.903

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

GnomAD4 genome AF: 0.907 AC: 137841 AN: 152046 Hom.: 62709 Cov.: 30 AF XY: 0.906 AC XY: 67337 AN XY: 74318

Gnomad4 AFR AF: 0.976

Gnomad4 AMR AF: 0.869

Gnomad4 ASJ AF: 0.852

Gnomad4 EAS AF: 0.764

Gnomad4 SAS AF: 0.828

Gnomad4 FIN AF: 0.920

Gnomad4 NFE AF: 0.890

Gnomad4 OTH AF: 0.904

Alfa AF: 0.889 Hom.: 30398

Bravo AF: 0.908

Asia WGS AF: 0.813 AC: 2828 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.33
CADD	Benign	20
DANN	Benign	0.85

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: rs13149511; hg19: chr4-25358109;