Genetic Variant ENST00000401392.5:c.-185G>A (chr2-135530703-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000401392.5(ZRANB3):c.-185G>A variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.308 in 152,194 control chromosomes in the GnomAD database, including 11,174 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 0.31 ( 11174 hom., cov: 32)

Exomes 𝑓: 0.094 ( 0 hom. )

Consequence

ZRANB3
ENST00000401392.5 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.197

Publications

14 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=-0.78).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.646 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000401392.5. 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.-8+424G>A	intron	N/A	NP_115519.2	Q5FWF4-1
ZRANB3	NM_001286569.1		c.-1670G>A	5_prime_UTR_premature_start_codon_gain	Exon 1 of 22	NP_001273498.1	F5GYN7
ZRANB3	NM_001286569.1		c.-1670G>A	5_prime_UTR	Exon 1 of 22	NP_001273498.1	F5GYN7

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ZRANB3	ENST00000401392.5	TSL:1	c.-185G>A	5_prime_UTR_premature_start_codon_gain	Exon 1 of 21	ENSP00000383979.1	Q5FWF4-3
ZRANB3	ENST00000536680.5	TSL:1	c.-1670G>A	5_prime_UTR_premature_start_codon_gain	Exon 1 of 22	ENSP00000441320.2	F5GYN7
ZRANB3	ENST00000401392.5	TSL:1	c.-185G>A	5_prime_UTR	Exon 1 of 21	ENSP00000383979.1	Q5FWF4-3

Frequencies

GnomAD3 genomes

AF:

0.307

AC:

46752

AN:

152044

Hom.:

11129

Cov.:

show subpopulations

Gnomad AFR

AF:

0.651

Gnomad AMI

AF:

0.0800

Gnomad AMR

AF:

0.323

Gnomad ASJ

AF:

0.245

Gnomad EAS

AF:

0.221

Gnomad SAS

AF:

0.381

Gnomad FIN

AF:

0.138

Gnomad MID

AF:

0.247

Gnomad NFE

AF:

0.130

Gnomad OTH

AF:

0.286

GnomAD4 exome

AF:

0.0938

AC:

AN:

Hom.:

Cov.:

AF XY:

0.0769

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AF:

0.500

AC:

AN:

European-Non Finnish (NFE)

AF:

0.100

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.308

AC:

46855

AN:

152162

Hom.:

11174

Cov.:

AF XY:

0.310

AC XY:

23079

AN XY:

74394

show subpopulations

African (AFR)

AF:

0.652

AC:

27041

AN:

41466

American (AMR)

AF:

0.323

AC:

4933

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.245

AC:

850

AN:

3470

East Asian (EAS)

AF:

0.221

AC:

1145

AN:

5178

South Asian (SAS)

AF:

0.380

AC:

1830

AN:

4822

European-Finnish (FIN)

AF:

0.138

AC:

1465

AN:

10610

Middle Eastern (MID)

AF:

0.245

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.130

AC:

8839

AN:

68004

Other (OTH)

AF:

0.287

AC:

607

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1272

2544

3817

5089

6361

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

410

820

1230

1640

2050

<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:

0.204

Hom.:

15196

Bravo

AF:

0.333

Asia WGS

AF:

0.335

AC:

1166

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

3.8

(source)

DANN

Benign

0.75

PhyloP100

-0.20

PromoterAI

0.023

Neutral

(source)

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