rs2118395

Variant names:

• chr2-135443750-A-T
• rs2118395
• NM_032143.4:c.162-52930T>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_032143.4(ZRANB3):​c.162-52930T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.104 in 152,144 control chromosomes in the GnomAD database, including 1,088 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 0.10 (1088 hom., cov: 32)
• Consequence: ZRANB3 NM_032143.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.498
• Publications: 1 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.303 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZRANB3	NM_032143.4	c.162-52930T>A		intron_variant	Intron 2 of 20	ENST00000264159.11	NP_115519.2
ZRANB3	NM_001286568.2	c.162-52930T>A		intron_variant	Intron 2 of 20		NP_001273497.1
ZRANB3	NM_001286569.1	c.-1296-52930T>A		intron_variant	Intron 2 of 21		NP_001273498.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZRANB3	ENST00000264159.11	c.162-52930T>A		intron_variant	Intron 2 of 20	1	NM_032143.4	ENSP00000264159.6

Frequencies

GnomAD3 genomes AF: 0.104 AC: 15827 AN: 152026 Hom.: 1092 Cov.: 32

Gnomad AFR AF: 0.0907

Gnomad AMI AF: 0.0811

Gnomad AMR AF: 0.195

Gnomad ASJ AF: 0.128

Gnomad EAS AF: 0.162

Gnomad SAS AF: 0.318

Gnomad FIN AF: 0.0625

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.0767

Gnomad OTH AF: 0.128

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

GnomAD4 genome AF: 0.104 AC: 15833 AN: 152144 Hom.: 1088 Cov.: 32 AF XY: 0.109 AC XY: 8133 AN XY: 74374

African (AFR) AF: 0.0909 AC: 3770 AN: 41496

American (AMR) AF: 0.195 AC: 2981 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.128 AC: 446 AN: 3472

East Asian (EAS) AF: 0.162 AC: 835 AN: 5168

South Asian (SAS) AF: 0.317 AC: 1520 AN: 4802

European-Finnish (FIN) AF: 0.0625 AC: 662 AN: 10596

Middle Eastern (MID) AF: 0.184 AC: 54 AN: 294

European-Non Finnish (NFE) AF: 0.0767 AC: 5218 AN: 68008

Other (OTH) AF: 0.129 AC: 273 AN: 2114

Alfa AF: 0.0876 Hom.: 86

Bravo AF: 0.109

Asia WGS AF: 0.248 AC: 860 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	7.0
DANN	Benign	0.89
PhyloP100		0.50
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2118395; hg19: chr2-136201320;