chr2-135429682-T-C

Variant names:

• chr2-135429682-T-C
• rs4954256
• NM_032143.4:c.162-38862A>G

Variant summary

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

The NM_032143.4(ZRANB3):​c.162-38862A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.267 in 151,874 control chromosomes in the GnomAD database, including 9,076 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 (9076 hom., cov: 31)
• Consequence: ZRANB3 NM_032143.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.861
• Publications: 8 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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.595 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZRANB3	NM_032143.4	MANE Select	c.162-38862A>G		intron	N/A	NP_115519.2
	ZRANB3	NM_001286568.2		c.162-38862A>G		intron	N/A	NP_001273497.1
	ZRANB3	NM_001286569.1		c.-1296-38862A>G		intron	N/A	NP_001273498.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZRANB3	ENST00000264159.11	TSL:1 MANE Select	c.162-38862A>G		intron	N/A	ENSP00000264159.6
	ZRANB3	ENST00000401392.5	TSL:1	c.162-38862A>G		intron	N/A	ENSP00000383979.1
	ZRANB3	ENST00000536680.5	TSL:1	c.-1296-38862A>G		intron	N/A	ENSP00000441320.2

Frequencies

GnomAD3 genomes AF: 0.267 AC: 40502 AN: 151756 Hom.: 9050 Cov.: 31

Gnomad AFR AF: 0.601

Gnomad AMI AF: 0.0795

Gnomad AMR AF: 0.276

Gnomad ASJ AF: 0.193

Gnomad EAS AF: 0.218

Gnomad SAS AF: 0.336

Gnomad FIN AF: 0.0753

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.0976

Gnomad OTH AF: 0.249

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

GnomAD4 genome AF: 0.267 AC: 40578 AN: 151874 Hom.: 9076 Cov.: 31 AF XY: 0.268 AC XY: 19865 AN XY: 74252

African (AFR) AF: 0.602 AC: 24873 AN: 41346

American (AMR) AF: 0.276 AC: 4208 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.193 AC: 669 AN: 3468

East Asian (EAS) AF: 0.218 AC: 1127 AN: 5172

South Asian (SAS) AF: 0.334 AC: 1606 AN: 4812

European-Finnish (FIN) AF: 0.0753 AC: 795 AN: 10560

Middle Eastern (MID) AF: 0.224 AC: 66 AN: 294

European-Non Finnish (NFE) AF: 0.0976 AC: 6634 AN: 67968

Other (OTH) AF: 0.251 AC: 528 AN: 2106

Alfa AF: 0.164 Hom.: 1078

Bravo AF: 0.293

Asia WGS AF: 0.310 AC: 1079 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	5.5
DANN	Benign	0.65
PhyloP100		-0.86
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: rs4954256; hg19: chr2-136187252;