rs7608637

Positions:

• chr2-135337935-A-C
• chr2-135337935-A-G

Variant summary

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

The NM_032143.4(ZRANB3):​c.677+7615T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.265 in 152,092 control chromosomes in the GnomAD database, including 8,872 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 0.26 (8872 hom., cov: 32)
• Consequence: ZRANB3 NM_032143.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0680

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]

ZRANB3 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.587 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZRANB3	NM_032143.4	c.677+7615T>G		intron_variant		ENST00000264159.11	NP_115519.2
ZRANB3	NM_001286568.2	c.677+7615T>G		intron_variant			NP_001273497.1
ZRANB3	NM_001286569.1	c.-781+7615T>G		intron_variant			NP_001273498.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZRANB3	ENST00000264159.11	c.677+7615T>G		intron_variant		1	NM_032143.4	ENSP00000264159.6

Frequencies

GnomAD3 genomes AF: 0.264 AC: 40164 AN: 151974 Hom.: 8843 Cov.: 32

Gnomad AFR AF: 0.592

Gnomad AMI AF: 0.0800

Gnomad AMR AF: 0.275

Gnomad ASJ AF: 0.193

Gnomad EAS AF: 0.218

Gnomad SAS AF: 0.335

Gnomad FIN AF: 0.0751

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.0975

Gnomad OTH AF: 0.247

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

GnomAD4 genome AF: 0.265 AC: 40244 AN: 152092 Hom.: 8872 Cov.: 32 AF XY: 0.265 AC XY: 19711 AN XY: 74374

Gnomad4 AFR AF: 0.593

Gnomad4 AMR AF: 0.275

Gnomad4 ASJ AF: 0.193

Gnomad4 EAS AF: 0.218

Gnomad4 SAS AF: 0.333

Gnomad4 FIN AF: 0.0751

Gnomad4 NFE AF: 0.0975

Gnomad4 OTH AF: 0.249

Alfa AF: 0.0828 Hom.: 179

Bravo AF: 0.290

Asia WGS AF: 0.310 AC: 1077 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	2.7
DANN	Benign	0.86

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: rs7608637; hg19: chr2-136095505;