rs1370533

Positions:

• chr2-135492715-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.161+11614G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.265 in 151,876 control chromosomes in the GnomAD database, including 8,885 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 (8885 hom., cov: 31)
• Consequence: ZRANB3 NM_032143.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0850

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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.588 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZRANB3	NM_032143.4	c.161+11614G>A		intron_variant		ENST00000264159.11	NP_115519.2
ZRANB3	NM_001286568.2	c.161+11614G>A		intron_variant			NP_001273497.1
ZRANB3	NM_001286569.1	c.-1297+11614G>A		intron_variant			NP_001273498.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZRANB3	ENST00000264159.11	c.161+11614G>A		intron_variant		1	NM_032143.4	ENSP00000264159	P4

Frequencies

GnomAD3 genomes AF: 0.265 AC: 40205 AN: 151758 Hom.: 8861 Cov.: 31

Gnomad AFR AF: 0.594

Gnomad AMI AF: 0.0811

Gnomad AMR AF: 0.275

Gnomad ASJ AF: 0.193

Gnomad EAS AF: 0.218

Gnomad SAS AF: 0.336

Gnomad FIN AF: 0.0758

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.0976

Gnomad OTH AF: 0.248

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

GnomAD4 genome AF: 0.265 AC: 40279 AN: 151876 Hom.: 8885 Cov.: 31 AF XY: 0.266 AC XY: 19755 AN XY: 74260

Gnomad4 AFR AF: 0.595

Gnomad4 AMR AF: 0.275

Gnomad4 ASJ AF: 0.193

Gnomad4 EAS AF: 0.218

Gnomad4 SAS AF: 0.334

Gnomad4 FIN AF: 0.0758

Gnomad4 NFE AF: 0.0975

Gnomad4 OTH AF: 0.250

Alfa AF: 0.165 Hom.: 1156

Bravo AF: 0.291

Asia WGS AF: 0.310 AC: 1079 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.80
DANN	Benign	0.23

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: rs1370533; hg19: chr2-136250285;