2-135216198-A-G

Variant names:

• chr2-135216198-A-G
• rs16831455
• NM_032143.4:c.2495+1267T>C

Variant summary

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

The NM_032143.4(ZRANB3):​c.2495+1267T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.23 in 151,936 control chromosomes in the GnomAD database, including 6,046 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 0.23 (6046 hom., cov: 31)
• Consequence: ZRANB3 NM_032143.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.516

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.467 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZRANB3	NM_032143.4	c.2495+1267T>C		intron_variant	Intron 17 of 20	ENST00000264159.11	NP_115519.2
ZRANB3	NM_001286568.2	c.2489+1267T>C		intron_variant	Intron 17 of 20		NP_001273497.1
ZRANB3	NM_001286569.1	c.1133+1267T>C		intron_variant	Intron 18 of 21		NP_001273498.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZRANB3	ENST00000264159.11	c.2495+1267T>C		intron_variant	Intron 17 of 20	1	NM_032143.4	ENSP00000264159.6

Frequencies

GnomAD3 genomes AF: 0.229 AC: 34831 AN: 151818 Hom.: 6032 Cov.: 31

Gnomad AFR AF: 0.473

Gnomad AMI AF: 0.0815

Gnomad AMR AF: 0.261

Gnomad ASJ AF: 0.188

Gnomad EAS AF: 0.221

Gnomad SAS AF: 0.329

Gnomad FIN AF: 0.0748

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.0969

Gnomad OTH AF: 0.226

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

GnomAD4 genome AF: 0.230 AC: 34881 AN: 151936 Hom.: 6046 Cov.: 31 AF XY: 0.230 AC XY: 17096 AN XY: 74272

Gnomad4 AFR AF: 0.472

Gnomad4 AMR AF: 0.261

Gnomad4 ASJ AF: 0.188

Gnomad4 EAS AF: 0.221

Gnomad4 SAS AF: 0.327

Gnomad4 FIN AF: 0.0748

Gnomad4 NFE AF: 0.0969

Gnomad4 OTH AF: 0.227

Alfa AF: 0.116 Hom.: 636

Bravo AF: 0.250

Asia WGS AF: 0.298 AC: 1037 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	7.2
DANN	Benign	0.50

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: rs16831455; hg19: chr2-135973768;