10-124943817-C-A

Variant names:

• chr10-124943817-C-A
• rs10901841
• NM_017580.3:c.814+510C>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_017580.3(ZRANB1):​c.814+510C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.594 in 152,018 control chromosomes in the GnomAD database, including 30,461 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 0.59 (30461 hom., cov: 32)
• Consequence: ZRANB1 NM_017580.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.636
• Publications: 3 publications found

Genes affected

ZRANB1 (HGNC:18224): (zinc finger RANBP2-type containing 1) Enables K63-linked polyubiquitin modification-dependent protein binding activity and thiol-dependent deubiquitinase. Involved in several processes, including positive regulation of Wnt signaling pathway; protein deubiquitination; and regulation of cell morphogenesis. Located in cytosol and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.27).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.747 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZRANB1	NM_017580.3	c.814+510C>A		intron_variant	Intron 1 of 8	ENST00000359653.4	NP_060050.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZRANB1	ENST00000359653.4	c.814+510C>A		intron_variant	Intron 1 of 8	1	NM_017580.3	ENSP00000352676.4

Frequencies

GnomAD3 genomes AF: 0.594 AC: 90223 AN: 151900 Hom.: 30472 Cov.: 32

Gnomad AFR AF: 0.255

Gnomad AMI AF: 0.912

Gnomad AMR AF: 0.548

Gnomad ASJ AF: 0.824

Gnomad EAS AF: 0.742

Gnomad SAS AF: 0.712

Gnomad FIN AF: 0.726

Gnomad MID AF: 0.737

Gnomad NFE AF: 0.752

Gnomad OTH AF: 0.625

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

GnomAD4 genome AF: 0.594 AC: 90223 AN: 152018 Hom.: 30461 Cov.: 32 AF XY: 0.594 AC XY: 44132 AN XY: 74278

African (AFR) AF: 0.255 AC: 10548 AN: 41422

American (AMR) AF: 0.547 AC: 8353 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.824 AC: 2858 AN: 3470

East Asian (EAS) AF: 0.742 AC: 3831 AN: 5164

South Asian (SAS) AF: 0.712 AC: 3431 AN: 4816

European-Finnish (FIN) AF: 0.726 AC: 7681 AN: 10578

Middle Eastern (MID) AF: 0.748 AC: 220 AN: 294

European-Non Finnish (NFE) AF: 0.752 AC: 51148 AN: 67992

Other (OTH) AF: 0.625 AC: 1321 AN: 2112

Alfa AF: 0.715 Hom.: 17430

Bravo AF: 0.563

Asia WGS AF: 0.682 AC: 2372 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.27
CADD	Benign	18
DANN	Benign	0.80
PhyloP100		0.64
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10901841; hg19: chr10-126632386;