rs1561277

Positions:

• chr2-135334491-C-A
• chr2-135334491-C-G
• chr2-135334491-C-T

Variant summary

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

The NM_032143.4(ZRANB3):​c.677+11059G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.578 in 152,062 control chromosomes in the GnomAD database, including 30,916 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 0.58 (30916 hom., cov: 32)
• Consequence: ZRANB3 NM_032143.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.01

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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.974 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZRANB3	NM_032143.4	c.677+11059G>T		intron_variant		ENST00000264159.11
ZRANB3	NM_001286568.2	c.677+11059G>T		intron_variant
ZRANB3	NM_001286569.1	c.-781+11059G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZRANB3	ENST00000264159.11	c.677+11059G>T		intron_variant		1	NM_032143.4	P4

Frequencies

GnomAD3 genomes AF: 0.578 AC: 87753 AN: 151944 Hom.: 30854 Cov.: 32

Gnomad AFR AF: 0.875

Gnomad AMI AF: 0.281

Gnomad AMR AF: 0.718

Gnomad ASJ AF: 0.817

Gnomad EAS AF: 0.997

Gnomad SAS AF: 0.747

Gnomad FIN AF: 0.355

Gnomad MID AF: 0.902

Gnomad NFE AF: 0.344

Gnomad OTH AF: 0.656

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

GnomAD4 genome AF: 0.578 AC: 87879 AN: 152062 Hom.: 30916 Cov.: 32 AF XY: 0.590 AC XY: 43857 AN XY: 74310

Gnomad4 AFR AF: 0.875

Gnomad4 AMR AF: 0.718

Gnomad4 ASJ AF: 0.817

Gnomad4 EAS AF: 0.997

Gnomad4 SAS AF: 0.746

Gnomad4 FIN AF: 0.355

Gnomad4 NFE AF: 0.344

Gnomad4 OTH AF: 0.660

Alfa AF: 0.404 Hom.: 7312

Bravo AF: 0.616

Asia WGS AF: 0.893 AC: 3104 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	8.8
DANN	Benign	0.67

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: rs1561277; hg19: chr2-136092061;