chr2-135258944-C-T

Position:

• chr2-135258944-C-T

Variant summary

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

The ENST00000264159.11(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 ENST00000264159.11 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.172

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=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.335 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZRANB3	NM_032143.4	c.1539+6590G>A		intron_variant		ENST00000264159.11	NP_115519.2
ZRANB3	NM_001286568.2	c.1539+6590G>A		intron_variant			NP_001273497.1
ZRANB3	NM_001286569.1	c.177+6590G>A		intron_variant			NP_001273498.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZRANB3	ENST00000264159.11	c.1539+6590G>A		intron_variant		1	NM_032143.4	ENSP00000264159	P4
ZRANB3	ENST00000401392.5	c.1539+6590G>A		intron_variant		1		ENSP00000383979	A2
ZRANB3	ENST00000536680.5	c.177+6590G>A		intron_variant		1		ENSP00000441320
ZRANB3	ENST00000403017.2	c.*347+6590G>A		intron_variant, NMD_transcript_variant		5		ENSP00000384245

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

Gnomad4 AFR AF: 0.340

Gnomad4 AMR AF: 0.249

Gnomad4 ASJ AF: 0.188

Gnomad4 EAS AF: 0.222

Gnomad4 SAS AF: 0.333

Gnomad4 FIN AF: 0.0752

Gnomad4 NFE AF: 0.0978

Gnomad4 OTH AF: 0.207

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.9
DANN	Benign	0.45

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: rs4954231; hg19: chr2-136016514;