dbSNP rs737388: ZRANB3:c.678-111A>G (chr2-135315641-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_032143.4(ZRANB3):c.678-111A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0305 in 787,776 control chromosomes in the GnomAD database, including 989 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 0.062 ( 577 hom., cov: 32)

Exomes 𝑓: 0.023 ( 412 hom. )

Consequence

ZRANB3
NM_032143.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0360

Publications

3 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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ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.158 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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ZRANB3	NM_032143.4	MANE Select	c.678-111A>G	intron	N/A	NP_115519.2	Q5FWF4-1
ZRANB3	NM_001286568.2		c.678-111A>G	intron	N/A	NP_001273497.1	Q5FWF4-3
ZRANB3	NM_001286569.1		c.-780-111A>G	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.678-111A>G	intron	N/A	ENSP00000264159.6	Q5FWF4-1
ZRANB3	ENST00000401392.5	TSL:1	c.678-111A>G	intron	N/A	ENSP00000383979.1	Q5FWF4-3
ZRANB3	ENST00000536680.5	TSL:1	c.-780-111A>G	intron	N/A	ENSP00000441320.2	F5GYN7

Frequencies

GnomAD3 genomes

AF:

0.0620

AC:

9429

AN:

152172

Hom.:

577

Cov.:

show subpopulations

Gnomad AFR

AF:

0.161

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0406

Gnomad ASJ

AF:

0.0599

Gnomad EAS

AF:

0.0561

Gnomad SAS

AF:

0.00993

Gnomad FIN

AF:

0.0128

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.0198

Gnomad OTH

AF:

0.0513

GnomAD4 exome

AF:

0.0229

AC:

14552

AN:

635486

Hom.:

412

AF XY:

0.0229

AC XY:

7268

AN XY:

317788

show subpopulations

African (AFR)

AF:

0.162

AC:

2230

AN:

13736

American (AMR)

AF:

0.0364

AC:

368

AN:

10104

Ashkenazi Jewish (ASJ)

AF:

0.0685

AC:

912

AN:

13320

East Asian (EAS)

AF:

0.0528

AC:

1391

AN:

26326

South Asian (SAS)

AF:

0.0105

AC:

302

AN:

28854

European-Finnish (FIN)

AF:

0.0154

AC:

471

AN:

30620

Middle Eastern (MID)

AF:

0.0285

AC:

AN:

2214

European-Non Finnish (NFE)

AF:

0.0162

AC:

7768

AN:

479686

Other (OTH)

AF:

0.0342

AC:

1047

AN:

30626

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

653

1305

1958

2610

3263

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

240

480

720

960

1200

<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:

0.0620

AC:

9446

AN:

152290

Hom.:

577

Cov.:

AF XY:

0.0601

AC XY:

4479

AN XY:

74474

show subpopulations

African (AFR)

AF:

0.161

AC:

6679

AN:

41538

American (AMR)

AF:

0.0407

AC:

622

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.0599

AC:

208

AN:

3472

East Asian (EAS)

AF:

0.0562

AC:

292

AN:

5192

South Asian (SAS)

AF:

0.00994

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.0128

AC:

136

AN:

10624

Middle Eastern (MID)

AF:

0.0238

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0198

AC:

1345

AN:

68024

Other (OTH)

AF:

0.0517

AC:

109

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

439

877

1316

1754

2193

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

184

276

368

460

<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:

0.0459

Hom.:

Bravo

AF:

0.0685

Asia WGS

AF:

0.0330

AC:

115

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

6.7

(source)

DANN

Benign

0.77

PhyloP100

-0.036

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over