chr2-135183933-A-G

Variant names:

• chr2-135183933-A-G
• rs935612
• ENST00000412849.5:n.1781+16421T>C

Variant summary

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

The ENST00000412849.5(ZRANB3):​n.1781+16421T>C variant causes a intron 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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.682
• Publications: 2 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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.597 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000412849.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZRANB3	ENST00000412849.5	TSL:1	n.1781+16421T>C		intron	N/A
	ZRANB3	ENST00000619650.4	TSL:5	c.1617+16421T>C		intron	N/A	ENSP00000480120.1	Q5FWF4-2

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

African (AFR) AF: 0.603 AC: 24998 AN: 41450

American (AMR) AF: 0.278 AC: 4244 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.193 AC: 670 AN: 3470

East Asian (EAS) AF: 0.223 AC: 1159 AN: 5186

South Asian (SAS) AF: 0.337 AC: 1621 AN: 4816

European-Finnish (FIN) AF: 0.0738 AC: 783 AN: 10616

Middle Eastern (MID) AF: 0.221 AC: 65 AN: 294

European-Non Finnish (NFE) AF: 0.0993 AC: 6752 AN: 67998

Other (OTH) AF: 0.258 AC: 544 AN: 2110

Alfa AF: 0.179 Hom.: 1621

Bravo AF: 0.295

Asia WGS AF: 0.315 AC: 1094 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.53
DANN	Benign	0.50
PhyloP100		-0.68

Splicing

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

Other links and lift over

dbSNP: rs935612; hg19: chr2-135941503;