dbSNP rs4954228: ZRANB3:c.2352+149T>C (chr2-135218928-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is The variant received -12 classification points (ACMG Germline Pathogenicity v2019). BA1BP4_Strong

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 cumulative frequency of 0.177 (AC=97,154) in the gnomAD database across 549,536 control chromosomes, including 15,622 homozygotes. The grpmax filtering allele frequency (95% CI) is 0.597. In-silico predictor (BayesDel (noAF)) classifies this variant as likely benign. Splicing prediction tools (SpliceAI) predict no significant impact on normal splicing. 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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.09

Publications

4 publications found

Variant links:

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 links:

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new If you want to explore the variant's impact on the transcript NM_032143.4, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

Classification according to ACMG Germline Pathogenicity v2019

Classification was made for transcript

Our verdict: Benign. The variant received -12 points.

BP4

Computational evidence supports benign — no pathogenic computational or splicing signal (BP4); Splicing verdict: benign (Strong).; Germline computational verdict: benign (Strong).

BA1

GnomAD effective popmax AF >5% — BA1 stand-alone benign; GnomAD reliable popmax AF = 0.5974 — exceeds 5%% threshold (BA1 applied)

Variant Effect in Transcripts

Automated classification analysis was done for transcript: NM_032143.4. You can select a different transcript below to see updated classification assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ZRANB3	NM_032143.4	MANE Select	c.2352+149T>C	intron	N/A	NP_115519.2	Q5FWF4-1
ZRANB3	NM_001286568.2		c.2346+149T>C	intron	N/A	NP_001273497.1	Q5FWF4-3
ZRANB3	NM_001286569.1		c.990+149T>C	intron	N/A	NP_001273498.1	F5GYN7

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ZRANB3	ENST00000264159.11	TSL:1 MANE Select	c.2352+149T>C	intron	N/A	ENSP00000264159.6	Q5FWF4-1
ZRANB3	ENST00000401392.5	TSL:1	c.2346+149T>C	intron	N/A	ENSP00000383979.1	Q5FWF4-3
ZRANB3	ENST00000536680.5	TSL:1	c.990+149T>C	intron	N/A	ENSP00000441320.2	F5GYN7

Frequencies

GnomAD3 genomes

AF:

0.268

AC:

40813

AN:

152060

Hom.:

9160

Cov.:

show subpopulations

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

show subpopulations

African (AFR)

AF:

0.606

AC:

5469

AN:

9024

American (AMR)

AF:

0.266

AC:

2685

AN:

10088

Ashkenazi Jewish (ASJ)

AF:

0.194

AC:

2280

AN:

11774

East Asian (EAS)

AF:

0.218

AC:

5359

AN:

24616

South Asian (SAS)

AF:

0.297

AC:

8124

AN:

27352

European-Finnish (FIN)

AF:

0.0767

AC:

3032

AN:

39538

Middle Eastern (MID)

AF:

0.236

AC:

406

AN:

1718

European-Non Finnish (NFE)

AF:

0.0999

AC:

25025

AN:

250436

Other (OTH)

AF:

0.170

AC:

3882

AN:

22812

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.514

Heterozygous variant carriers

2018

4036

6053

8071

10089

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

268

536

804

1072

1340

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.269

AC:

40892

AN:

152178

Hom.:

9188

Cov.:

AF XY:

0.269

AC XY:

20009

AN XY:

74420

show subpopulations

African (AFR)

AF:

0.604

AC:

25040

AN:

41480

American (AMR)

AF:

0.277

AC:

4235

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.193

AC:

670

AN:

3470

East Asian (EAS)

AF:

0.223

AC:

1152

AN:

5176

South Asian (SAS)

AF:

0.334

AC:

1609

AN:

4818

European-Finnish (FIN)

AF:

0.0752

AC:

798

AN:

10612

Middle Eastern (MID)

AF:

0.218

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0987

AC:

6713

AN:

68018

Other (OTH)

AF:

0.255

AC:

537

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.517

Heterozygous variant carriers

1190

2381

3571

4762

5952

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

362

724

1086

1448

1810

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.150

Hom.:

1828

Bravo

AF:

0.294

Asia WGS

AF:

0.313

AC:

1088

AN:

3478

Local populations

ToMMo 61KJPN (+60KJPN MNV)

AF:

0.218

AC:

26733

AN:

122800

Turkish Variome

AF:

0.248

AC:

383

AN:

1546

Hom.:

WBBC (Westlake BioBank for Chinese) pilot

AF:

0.208

AC:

1864

AN:

8960

Hom.:

184

ABraOM SABE-WGS-1171

AF:

0.283

AC:

662

AN:

2342

Hom.:

121

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

3.8

(source)

DANN

Benign

0.44

PhyloP100

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

Classification according to ACMG Germline Pathogenicity v2019

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

Local populations

ClinVar

Computational scores

Splicing

Publications

Other links and lift over