Genetic Variant NM_001371189.2:c.*810G>A (chr9-35404843-G-A) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_ModerateBA1

The NM_001371189.2(UNC13B):c.*810G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.163 in 152,600 control chromosomes in the GnomAD database, including 2,798 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 0.16 ( 2778 hom., cov: 31)

Exomes 𝑓: 0.25 ( 20 hom. )

Consequence

UNC13B
NM_001371189.2 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.487

Publications

11 publications found

Variant links:

Genes affected

UNC13B (HGNC:12566): (unc-13 homolog B) This gene is expressed in the kidney cortical epithelial cells and is upregulated by hyperglycemia. The encoded protein shares a high level of similarity to the rat homolog, and contains 3 C2 domains and a diacylglycerol-binding C1 domain. Hyperglycemia increases the levels of diacylglycerol, which has been shown to induce apoptosis in cells transfected with this gene and thus contribute to the renal cell complications of hyperglycemia. Studies in other species also indicate a role for this protein in the priming step of synaptic vesicle exocytosis. [provided by RefSeq, Jul 2008]

UNC13B links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.36).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.235 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001371189.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
UNC13B	NM_001371189.2	MANE Select	c.*810G>A	3_prime_UTR	Exon 40 of 40	NP_001358118.1
UNC13B	NR_170667.1		n.5947G>A	non_coding_transcript_exon	Exon 42 of 42
UNC13B	NM_001371187.2		c.*810G>A	3_prime_UTR	Exon 33 of 33	NP_001358116.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
UNC13B	ENST00000635942.2	TSL:5 MANE Select	c.*810G>A	3_prime_UTR	Exon 40 of 40	ENSP00000490228.1
UNC13B	ENST00000619578.4	TSL:1	c.*810G>A	3_prime_UTR	Exon 40 of 40	ENSP00000479261.1
UNC13B	ENST00000378495.7	TSL:1	c.*810G>A	3_prime_UTR	Exon 39 of 39	ENSP00000367756.3

Frequencies

GnomAD3 genomes

AF:

0.162

AC:

24699

AN:

152002

Hom.:

2778

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0419

Gnomad AMI

AF:

0.306

Gnomad AMR

AF:

0.160

Gnomad ASJ

AF:

0.247

Gnomad EAS

AF:

0.000578

Gnomad SAS

AF:

0.0451

Gnomad FIN

AF:

0.243

Gnomad MID

AF:

0.203

Gnomad NFE

AF:

0.238

Gnomad OTH

AF:

0.169

GnomAD4 exome

AF:

0.248

AC:

119

AN:

480

Hom.:

Cov.:

AF XY:

0.245

AC XY:

AN XY:

298

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.245

AC:

104

AN:

424

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.333

AC:

AN:

Other (OTH)

AF:

0.0833

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

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:

0.162

AC:

24694

AN:

152120

Hom.:

2778

Cov.:

AF XY:

0.159

AC XY:

11848

AN XY:

74364

show subpopulations

African (AFR)

AF:

0.0418

AC:

1734

AN:

41514

American (AMR)

AF:

0.159

AC:

2435

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.247

AC:

858

AN:

3470

East Asian (EAS)

AF:

0.000773

AC:

AN:

5174

South Asian (SAS)

AF:

0.0454

AC:

219

AN:

4828

European-Finnish (FIN)

AF:

0.243

AC:

2572

AN:

10572

Middle Eastern (MID)

AF:

0.201

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.238

AC:

16181

AN:

67962

Other (OTH)

AF:

0.167

AC:

354

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

997

1993

2990

3986

4983

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

254

508

762

1016

1270

<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:

0.215

Hom.:

6376

Bravo

AF:

0.151

Asia WGS

AF:

0.0270

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.36

CADD

Benign

5.9

(source)

DANN

Benign

0.83

PhyloP100

0.49

Mutation Taster

=99/1

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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