rs935612

Positions:

• chr2-135183933-A-G
• chr2-135183933-A-T

Variant summary

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

The ENST00000412849.5(ZRANB3):​n.1781+16421T>C variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.269 in 152,138 control chromosomes in the GnomAD database, including 9,152 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 0.27 (9152 hom., cov: 32)
• Consequence: ZRANB3 ENST00000412849.5 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.682

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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.597 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZRANB3	ENST00000412849.5	n.1781+16421T>C		intron_variant, non_coding_transcript_variant		1
ZRANB3	ENST00000619650.4	c.1617+16421T>C		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.269 AC: 40828 AN: 152020 Hom.: 9123 Cov.: 32

Gnomad AFR AF: 0.603

Gnomad AMI AF: 0.0793

Gnomad AMR AF: 0.278

Gnomad ASJ AF: 0.193

Gnomad EAS AF: 0.223

Gnomad SAS AF: 0.338

Gnomad FIN AF: 0.0738

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.0993

Gnomad OTH AF: 0.256

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

GnomAD4 genome AF: 0.269 AC: 40908 AN: 152138 Hom.: 9152 Cov.: 32 AF XY: 0.269 AC XY: 20003 AN XY: 74422

Gnomad4 AFR AF: 0.603

Gnomad4 AMR AF: 0.278

Gnomad4 ASJ AF: 0.193

Gnomad4 EAS AF: 0.223

Gnomad4 SAS AF: 0.337

Gnomad4 FIN AF: 0.0738

Gnomad4 NFE AF: 0.0993

Gnomad4 OTH AF: 0.258

Alfa AF: 0.169 Hom.: 1210

Bravo AF: 0.295

Asia WGS AF: 0.315 AC: 1094 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.53
DANN	Benign	0.50

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs935612; hg19: chr2-135941503;