Variant 1-153930573-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BS1BS2

The NM_014856.3(DENND4B):c.4311A>G(p.Thr1437Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00178 in 1,613,986 control chromosomes in the GnomAD database, including 44 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.0021 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0018 ( 43 hom. )

Consequence

DENND4B
NM_014856.3 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -2.94

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]

DENND4B links:

DENND4B (HGNC:):

DENND4B links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.75).

BP6

Variant 1-153930573-T-C is Benign according to our data. Variant chr1-153930573-T-C is described in ClinVar as [Benign]. Clinvar id is 3044596.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=-2.94 with no splicing effect.

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00208 (316/152278) while in subpopulation EAS AF= 0.0191 (99/5176). AF 95% confidence interval is 0.0161. There are 1 homozygotes in gnomad4. There are 163 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 316 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DENND4B	NM_014856.3 linkuse as main transcript	c.4311A>G	p.Thr1437Thr	synonymous_variant	27/28	ENST00000361217.9	NP_055671.2	O75064

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DENND4B	ENST00000361217.9 linkuse as main transcript	c.4311A>G	p.Thr1437Thr	synonymous_variant	27/28	1	NM_014856.3	ENSP00000354597.4		O75064

Frequencies

GnomAD3 genomes

AF:

0.00208

AC:

317

AN:

152160

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00995

Gnomad ASJ

AF:

0.00490

Gnomad EAS

AF:

0.0193

Gnomad SAS

AF:

0.00248

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000279

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.00394

AC:

982

AN:

249234

Hom.:

AF XY:

0.00338

AC XY:

457

AN XY:

135208

show subpopulations

Gnomad AFR exome

AF:

0.000129

Gnomad AMR exome

AF:

0.0101

Gnomad ASJ exome

AF:

0.00527

Gnomad EAS exome

AF:

0.0278

Gnomad SAS exome

AF:

0.00118

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000230

Gnomad OTH exome

AF:

0.00297

GnomAD4 exome

AF:

0.00175

AC:

2564

AN:

1461708

Hom.:

Cov.:

AF XY:

0.00171

AC XY:

1247

AN XY:

727136

show subpopulations

Gnomad4 AFR exome

AF:

0.000179

Gnomad4 AMR exome

AF:

0.0119

Gnomad4 ASJ exome

AF:

0.00440

Gnomad4 EAS exome

AF:

0.0378

Gnomad4 SAS exome

AF:

0.00121

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.000159

Gnomad4 OTH exome

AF:

0.00210

GnomAD4 genome

AF:

0.00208

AC:

316

AN:

152278

Hom.:

Cov.:

AF XY:

0.00219

AC XY:

163

AN XY:

74460

show subpopulations

Gnomad4 AFR

AF:

0.000241

Gnomad4 AMR

AF:

0.00994

Gnomad4 ASJ

AF:

0.00490

Gnomad4 EAS

AF:

0.0191

Gnomad4 SAS

AF:

0.00249

Gnomad4 FIN

AF:

0.0000942

Gnomad4 NFE

AF:

0.000279

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.00108

Hom.:

Bravo

AF:

0.00339

Asia WGS

AF:

0.00982

AC:

AN:

3478

EpiCase

AF:

0.000109

EpiControl

AF:

0.000237

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

DENND4B-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jun 19, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.75

CADD

Benign

0.49

DANN

Benign

0.71

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over