chr1-153930964-A-G
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Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 1P and 6B. PP2BP4_ModerateBS2
The NM_014856.3(DENND4B):āc.4097T>Cā(p.Val1366Ala) variant causes a missense change. The variant allele was found at a frequency of 0.0000261 in 1,608,496 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: š 0.000013 ( 0 hom., cov: 32)
Exomes š: 0.000027 ( 0 hom. )
Consequence
DENND4B
NM_014856.3 missense
NM_014856.3 missense
Scores
5
14
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 6.46
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]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -5 ACMG points.
PP2
Missense variant in gene, where missense usually causes diseases (based on misZ statistic), DENND4B. . Gene score misZ 3.2312 (greater than the threshold 3.09). Trascript score misZ 4.0136 (greater than threshold 3.09). GenCC has associacion of gene with isolated cleft palate.
BP4
Computational evidence support a benign effect (MetaRNN=0.14462054).
BS2
High AC in GnomAdExome4 at 40 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DENND4B | NM_014856.3 | c.4097T>C | p.Val1366Ala | missense_variant | 25/28 | ENST00000361217.9 | |
LOC101928059 | XR_922160.3 | n.924+2194A>G | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DENND4B | ENST00000361217.9 | c.4097T>C | p.Val1366Ala | missense_variant | 25/28 | 1 | NM_014856.3 | P1 | |
ENST00000641448.2 | n.815+2194A>G | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes AF: 0.0000133 AC: 2AN: 150032Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000163 AC: 4AN: 246058Hom.: 0 AF XY: 0.00000749 AC XY: 1AN XY: 133466
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GnomAD4 exome AF: 0.0000274 AC: 40AN: 1458340Hom.: 0 Cov.: 37 AF XY: 0.0000165 AC XY: 12AN XY: 725296
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GnomAD4 genome AF: 0.0000133 AC: 2AN: 150156Hom.: 0 Cov.: 32 AF XY: 0.0000136 AC XY: 1AN XY: 73368
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ClinVar
Not reported inComputational scores
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Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T
M_CAP
Benign
T
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Benign
L
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D
REVEL
Benign
Sift
Benign
T
Sift4G
Benign
T
Polyphen
B
Vest4
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MPC
ClinPred
D
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Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at