Variant 1-197617670-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_001195215.2(DENND1B):c.762G>A(p.Leu254Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00339 in 1,606,722 control chromosomes in the GnomAD database, including 151 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.018 ( 76 hom., cov: 32)

Exomes 𝑓: 0.0019 ( 75 hom. )

Consequence

DENND1B
NM_001195215.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 3.01

Variant links:

Genes affected

DENND1B (HGNC:28404): (DENN domain containing 1B) Clathrin (see MIM 118955)-mediated endocytosis is a major mechanism for internalization of proteins and lipids. Members of the connecdenn family, such as DENND1B, function as guanine nucleotide exchange factors (GEFs) for the early endosomal small GTPase RAB35 (MIM 604199) and bind to clathrin and clathrin adaptor protein-2 (AP2; see MIM 601024). Thus, connecdenns link RAB35 activation with the clathrin machinery (Marat and McPherson, 2010 [PubMed 20154091]).[supplied by OMIM, Nov 2010]

DENND1B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.32).

BP6

Variant 1-197617670-C-T is Benign according to our data. Variant chr1-197617670-C-T is described in ClinVar as [Benign]. Clinvar id is 781797.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=3.01 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0583 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DENND1B	NM_001195215.2 link	c.762G>A	p.Leu254Leu	synonymous_variant	11/23	ENST00000620048.6	NP_001182144.1	Q6P3S1-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DENND1B	ENST00000620048.6 link	c.762G>A	p.Leu254Leu	synonymous_variant	11/23	5	NM_001195215.2	ENSP00000479816.1		Q6P3S1-1

Frequencies

GnomAD3 genomes

AF:

0.0176

AC:

2659

AN:

151152

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0603

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00674

Gnomad ASJ

AF:

0.00203

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00637

Gnomad NFE

AF:

0.000400

Gnomad OTH

AF:

0.0149

GnomAD3 exomes

AF:

0.00449

AC:

1111

AN:

247332

Hom.:

AF XY:

0.00348

AC XY:

467

AN XY:

134182

show subpopulations

Gnomad AFR exome

AF:

0.0622

Gnomad AMR exome

AF:

0.00271

Gnomad ASJ exome

AF:

0.00110

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000655

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000375

Gnomad OTH exome

AF:

0.00201

GnomAD4 exome

AF:

0.00191

AC:

2784

AN:

1455452

Hom.:

Cov.:

AF XY:

0.00168

AC XY:

1215

AN XY:

724186

show subpopulations

Gnomad4 AFR exome

AF:

0.0613

Gnomad4 AMR exome

AF:

0.00326

Gnomad4 ASJ exome

AF:

0.00108

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000930

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000244

Gnomad4 OTH exome

AF:

0.00457

GnomAD4 genome

AF:

0.0176

AC:

2664

AN:

151270

Hom.:

Cov.:

AF XY:

0.0173

AC XY:

1280

AN XY:

73918

show subpopulations

Gnomad4 AFR

AF:

0.0602

Gnomad4 AMR

AF:

0.00674

Gnomad4 ASJ

AF:

0.00203

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000400

Gnomad4 OTH

AF:

0.0148

Alfa

AF:

0.00727

Hom.:

Bravo

AF:

0.0197

Asia WGS

AF:

0.00318

AC:

AN:

3478

EpiCase

AF:

0.000110

EpiControl

AF:

0.000774

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.32

CADD

Benign

DANN

Benign

0.70

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.14

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