rs4954259

Positions:

• chr2-135480424-G-A

Variant summary

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

The NM_032143.4(ZRANB3):​c.161+23905C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.105 in 151,982 control chromosomes in the GnomAD database, including 1,099 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 0.11 (1099 hom., cov: 30)
• Consequence: ZRANB3 NM_032143.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.89

Genes affected

ZRANB3 (HGNC:25249): (zinc finger RANBP2-type containing 3) Enables ATP-dependent DNA/DNA annealing activity; K63-linked polyubiquitin modification-dependent protein binding activity; and endodeoxyribonuclease activity. Involved in several processes, including DNA metabolic process; DNA rewinding; and negative regulation of DNA recombination. Located in nuclear replication fork and nucleoplasm. [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=-0.86).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.304 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZRANB3	NM_032143.4	c.161+23905C>T		intron_variant		ENST00000264159.11	NP_115519.2
ZRANB3	NM_001286568.2	c.161+23905C>T		intron_variant			NP_001273497.1
ZRANB3	NM_001286569.1	c.-1297+23905C>T		intron_variant			NP_001273498.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZRANB3	ENST00000264159.11	c.161+23905C>T		intron_variant		1	NM_032143.4	ENSP00000264159	P4

Frequencies

GnomAD3 genomes AF: 0.105 AC: 15950 AN: 151864 Hom.: 1103 Cov.: 30

Gnomad AFR AF: 0.0936

Gnomad AMI AF: 0.0811

Gnomad AMR AF: 0.196

Gnomad ASJ AF: 0.129

Gnomad EAS AF: 0.162

Gnomad SAS AF: 0.319

Gnomad FIN AF: 0.0626

Gnomad MID AF: 0.189

Gnomad NFE AF: 0.0767

Gnomad OTH AF: 0.129

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

GnomAD4 genome AF: 0.105 AC: 15960 AN: 151982 Hom.: 1099 Cov.: 30 AF XY: 0.110 AC XY: 8193 AN XY: 74288

Gnomad4 AFR AF: 0.0938

Gnomad4 AMR AF: 0.195

Gnomad4 ASJ AF: 0.129

Gnomad4 EAS AF: 0.162

Gnomad4 SAS AF: 0.317

Gnomad4 FIN AF: 0.0626

Gnomad4 NFE AF: 0.0767

Gnomad4 OTH AF: 0.130

Alfa AF: 0.0896 Hom.: 114

Bravo AF: 0.110

Asia WGS AF: 0.248 AC: 859 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.25
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: rs4954259; hg19: chr2-136237994;