2-135372221-A-G

Position:

• chr2-135372221-A-G

Variant summary

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

The NM_032143.4(ZRANB3):​c.180+18581T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.264 in 151,182 control chromosomes in the GnomAD database, including 8,778 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 0.26 (8778 hom., cov: 29)
• Consequence: ZRANB3 NM_032143.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.412

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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.586 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZRANB3	NM_032143.4	c.180+18581T>C		intron_variant		ENST00000264159.11	NP_115519.2
ZRANB3	NM_001286568.2	c.180+18581T>C		intron_variant			NP_001273497.1
ZRANB3	NM_001286569.1	c.-1278+18581T>C		intron_variant			NP_001273498.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZRANB3	ENST00000264159.11	c.180+18581T>C		intron_variant		1	NM_032143.4	ENSP00000264159	P4

Frequencies

GnomAD3 genomes AF: 0.263 AC: 39765 AN: 151070 Hom.: 8750 Cov.: 29

Gnomad AFR AF: 0.592

Gnomad AMI AF: 0.0811

Gnomad AMR AF: 0.274

Gnomad ASJ AF: 0.193

Gnomad EAS AF: 0.217

Gnomad SAS AF: 0.335

Gnomad FIN AF: 0.0742

Gnomad MID AF: 0.219

Gnomad NFE AF: 0.0963

Gnomad OTH AF: 0.245

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

GnomAD4 genome AF: 0.264 AC: 39843 AN: 151182 Hom.: 8778 Cov.: 29 AF XY: 0.264 AC XY: 19479 AN XY: 73798

Gnomad4 AFR AF: 0.592

Gnomad4 AMR AF: 0.274

Gnomad4 ASJ AF: 0.193

Gnomad4 EAS AF: 0.217

Gnomad4 SAS AF: 0.334

Gnomad4 FIN AF: 0.0742

Gnomad4 NFE AF: 0.0963

Gnomad4 OTH AF: 0.247

Alfa AF: 0.151 Hom.: 1441

Bravo AF: 0.289

Asia WGS AF: 0.309 AC: 1074 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.3
DANN	Benign	0.58

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: rs9798267; hg19: chr2-136129791;