rs7608637

Variant names:

• chr2-135337935-A-C
• rs7608637
• NM_032143.4:c.677+7615T>G

Your query was ambiguous. Multiple possible variants found:

• chr2-135337935-A-C
• chr2-135337935-A-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.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
• Publications: 2 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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.587 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZRANB3	NM_032143.4	MANE Select	c.677+7615T>G		intron	N/A	NP_115519.2	Q5FWF4-1
	ZRANB3	NM_001286568.2		c.677+7615T>G		intron	N/A	NP_001273497.1	Q5FWF4-3
	ZRANB3	NM_001286569.1		c.-781+7615T>G		intron	N/A	NP_001273498.1	F5GYN7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZRANB3	ENST00000264159.11	TSL:1 MANE Select	c.677+7615T>G		intron	N/A	ENSP00000264159.6	Q5FWF4-1
	ZRANB3	ENST00000401392.5	TSL:1	c.677+7615T>G		intron	N/A	ENSP00000383979.1	Q5FWF4-3
	ZRANB3	ENST00000536680.5	TSL:1	c.-781+7615T>G		intron	N/A	ENSP00000441320.2	F5GYN7

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

African (AFR) AF: 0.593 AC: 24551 AN: 41420

American (AMR) AF: 0.275 AC: 4202 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.193 AC: 668 AN: 3468

East Asian (EAS) AF: 0.218 AC: 1130 AN: 5176

South Asian (SAS) AF: 0.333 AC: 1606 AN: 4820

European-Finnish (FIN) AF: 0.0751 AC: 796 AN: 10602

Middle Eastern (MID) AF: 0.218 AC: 64 AN: 294

European-Non Finnish (NFE) AF: 0.0975 AC: 6628 AN: 68006

Other (OTH) AF: 0.249 AC: 526 AN: 2116

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	2.7
DANN	Benign	0.86
PhyloP100		-0.068
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: rs7608637; hg19: chr2-136095505;