2-135258944-C-T

Variant names:

• chr2-135258944-C-T
• rs4954231
• NM_032143.4:c.1539+6590G>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.1539+6590G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.193 in 152,156 control chromosomes in the GnomAD database, including 3,797 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 0.19 (3797 hom., cov: 32)
• Consequence: ZRANB3 NM_032143.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.172
• Publications: 7 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=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.335 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032143.4. 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
	ZRANB3	NM_032143.4	MANE Select	c.1539+6590G>A		intron	N/A	NP_115519.2
	ZRANB3	NM_001286568.2		c.1539+6590G>A		intron	N/A	NP_001273497.1
	ZRANB3	NM_001286569.1		c.177+6590G>A		intron	N/A	NP_001273498.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZRANB3	ENST00000264159.11	TSL:1 MANE Select	c.1539+6590G>A		intron	N/A	ENSP00000264159.6
	ZRANB3	ENST00000401392.5	TSL:1	c.1539+6590G>A		intron	N/A	ENSP00000383979.1
	ZRANB3	ENST00000536680.5	TSL:1	c.177+6590G>A		intron	N/A	ENSP00000441320.2

Frequencies

GnomAD3 genomes AF: 0.193 AC: 29269 AN: 152038 Hom.: 3785 Cov.: 32

Gnomad AFR AF: 0.339

Gnomad AMI AF: 0.0811

Gnomad AMR AF: 0.250

Gnomad ASJ AF: 0.188

Gnomad EAS AF: 0.222

Gnomad SAS AF: 0.334

Gnomad FIN AF: 0.0752

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.0978

Gnomad OTH AF: 0.205

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

GnomAD4 genome AF: 0.193 AC: 29318 AN: 152156 Hom.: 3797 Cov.: 32 AF XY: 0.196 AC XY: 14559 AN XY: 74408

African (AFR) AF: 0.340 AC: 14079 AN: 41460

American (AMR) AF: 0.249 AC: 3811 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.188 AC: 653 AN: 3470

East Asian (EAS) AF: 0.222 AC: 1151 AN: 5186

South Asian (SAS) AF: 0.333 AC: 1605 AN: 4824

European-Finnish (FIN) AF: 0.0752 AC: 797 AN: 10600

Middle Eastern (MID) AF: 0.207 AC: 61 AN: 294

European-Non Finnish (NFE) AF: 0.0978 AC: 6651 AN: 68022

Other (OTH) AF: 0.207 AC: 436 AN: 2110

Alfa AF: 0.115 Hom.: 617

Bravo AF: 0.208

Asia WGS AF: 0.298 AC: 1034 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.9
DANN	Benign	0.45
PhyloP100		0.17
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: rs4954231; hg19: chr2-136016514;