rs4954228

Positions:

• chr2-135218928-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.2352+149T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.177 in 549,536 control chromosomes in the GnomAD database, including 15,622 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 (9188 hom., cov: 32)
  • Exomes 𝑓: 0.14 (6434 hom.)
• Consequence: ZRANB3 NM_032143.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.09

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.597 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZRANB3	NM_032143.4	c.2352+149T>C		intron_variant		ENST00000264159.11	NP_115519.2
ZRANB3	NM_001286568.2	c.2346+149T>C		intron_variant			NP_001273497.1
ZRANB3	NM_001286569.1	c.990+149T>C		intron_variant			NP_001273498.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZRANB3	ENST00000264159.11	c.2352+149T>C		intron_variant		1	NM_032143.4	ENSP00000264159	P4

Frequencies

GnomAD3 genomes AF: 0.268 AC: 40813 AN: 152060 Hom.: 9160 Cov.: 32

Gnomad AFR AF: 0.603

Gnomad AMI AF: 0.0811

Gnomad AMR AF: 0.277

Gnomad ASJ AF: 0.193

Gnomad EAS AF: 0.222

Gnomad SAS AF: 0.336

Gnomad FIN AF: 0.0752

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.0987

Gnomad OTH AF: 0.253

GnomAD4 exome AF: 0.142 AC: 56262 AN: 397358 Hom.: 6434 AF XY: 0.148 AC XY: 30508 AN XY: 206432

Gnomad4 AFR exome AF: 0.606

Gnomad4 AMR exome AF: 0.266

Gnomad4 ASJ exome AF: 0.194

Gnomad4 EAS exome AF: 0.218

Gnomad4 SAS exome AF: 0.297

Gnomad4 FIN exome AF: 0.0767

Gnomad4 NFE exome AF: 0.0999

Gnomad4 OTH exome AF: 0.170

GnomAD4 genome AF: 0.269 AC: 40892 AN: 152178 Hom.: 9188 Cov.: 32 AF XY: 0.269 AC XY: 20009 AN XY: 74420

Gnomad4 AFR AF: 0.604

Gnomad4 AMR AF: 0.277

Gnomad4 ASJ AF: 0.193

Gnomad4 EAS AF: 0.223

Gnomad4 SAS AF: 0.334

Gnomad4 FIN AF: 0.0752

Gnomad4 NFE AF: 0.0987

Gnomad4 OTH AF: 0.255

Alfa AF: 0.149 Hom.: 1610

Bravo AF: 0.294

Asia WGS AF: 0.313 AC: 1088 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.8
DANN	Benign	0.44

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: rs4954228; hg19: chr2-135976498;