1-153941294-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_014856.3(DENND4B):​c.1123-5T>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.525 in 1,613,414 control chromosomes in the GnomAD database, including 231,295 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.58 ( 27167 hom., cov: 31)
Exomes 𝑓: 0.52 ( 204128 hom. )

Consequence

DENND4B
NM_014856.3 splice_region, intron

Scores

2
Splicing: ADA: 0.0001426
2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.168
Variant links:
Genes affected
DENND4B (HGNC:29044): (DENN domain containing 4B) Enables guanyl-nucleotide exchange factor activity. Involved in regulation of Rab protein signal transduction. Located in Golgi apparatus and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.82).
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.92 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
DENND4BNM_014856.3 linkc.1123-5T>C splice_region_variant, intron_variant Intron 7 of 27 ENST00000361217.9 NP_055671.2 O75064

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
DENND4BENST00000361217.9 linkc.1123-5T>C splice_region_variant, intron_variant Intron 7 of 27 1 NM_014856.3 ENSP00000354597.4 O75064
DENND4BENST00000368646.6 linkc.1156-5T>C splice_region_variant, intron_variant Intron 7 of 21 5 ENSP00000357635.2 E9PAK5
DENND4BENST00000483561.2 linkn.444-5T>C splice_region_variant, intron_variant Intron 2 of 2 4
DENND4BENST00000494683.1 linkn.62-5T>C splice_region_variant, intron_variant Intron 1 of 1 3

Frequencies

GnomAD3 genomes
AF:
0.584
AC:
88720
AN:
151842
Hom.:
27120
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.711
Gnomad AMI
AF:
0.499
Gnomad AMR
AF:
0.650
Gnomad ASJ
AF:
0.427
Gnomad EAS
AF:
0.942
Gnomad SAS
AF:
0.659
Gnomad FIN
AF:
0.559
Gnomad MID
AF:
0.557
Gnomad NFE
AF:
0.474
Gnomad OTH
AF:
0.563
GnomAD3 exomes
AF:
0.585
AC:
145571
AN:
248696
Hom.:
45059
AF XY:
0.578
AC XY:
78009
AN XY:
134938
show subpopulations
Gnomad AFR exome
AF:
0.717
Gnomad AMR exome
AF:
0.704
Gnomad ASJ exome
AF:
0.440
Gnomad EAS exome
AF:
0.942
Gnomad SAS exome
AF:
0.635
Gnomad FIN exome
AF:
0.552
Gnomad NFE exome
AF:
0.482
Gnomad OTH exome
AF:
0.554
GnomAD4 exome
AF:
0.519
AC:
758304
AN:
1461454
Hom.:
204128
Cov.:
63
AF XY:
0.520
AC XY:
378105
AN XY:
726994
show subpopulations
Gnomad4 AFR exome
AF:
0.724
Gnomad4 AMR exome
AF:
0.701
Gnomad4 ASJ exome
AF:
0.431
Gnomad4 EAS exome
AF:
0.946
Gnomad4 SAS exome
AF:
0.631
Gnomad4 FIN exome
AF:
0.549
Gnomad4 NFE exome
AF:
0.480
Gnomad4 OTH exome
AF:
0.546
GnomAD4 genome
AF:
0.585
AC:
88823
AN:
151960
Hom.:
27167
Cov.:
31
AF XY:
0.594
AC XY:
44107
AN XY:
74282
show subpopulations
Gnomad4 AFR
AF:
0.711
Gnomad4 AMR
AF:
0.651
Gnomad4 ASJ
AF:
0.427
Gnomad4 EAS
AF:
0.942
Gnomad4 SAS
AF:
0.659
Gnomad4 FIN
AF:
0.559
Gnomad4 NFE
AF:
0.474
Gnomad4 OTH
AF:
0.561
Alfa
AF:
0.515
Hom.:
12912
Bravo
AF:
0.601
Asia WGS
AF:
0.768
AC:
2670
AN:
3478
EpiCase
AF:
0.495
EpiControl
AF:
0.488

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.82
CADD
Benign
15
DANN
Benign
0.70

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.00014
dbscSNV1_RF
Benign
0.0
SpliceAI score (max)
0.10
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs2252508; hg19: chr1-153913770; API