Variant 7-44058434-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001014436.3(DBNL):c.707C>T(p.Thr236Met) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00224 in 1,614,198 control chromosomes in the GnomAD database, including 17 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0020 ( 5 hom., cov: 33)

Exomes 𝑓: 0.0023 ( 12 hom. )

Consequence

DBNL
NM_001014436.3 missense, splice_region

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.39

Variant links:

Genes affected

DBNL (HGNC:2696): (drebrin like) Enables cadherin binding activity. Predicted to be involved in several processes, including Rac protein signal transduction; nervous system development; and podosome assembly. Located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

DBNL links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0039149225).

BP6

Variant 7-44058434-C-T is Benign according to our data. Variant chr7-44058434-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2657418.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DBNL	NM_001014436.3 linkuse as main transcript	c.707C>T	p.Thr236Met	missense_variant, splice_region_variant	8/13	ENST00000448521.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DBNL	ENST00000448521.6 linkuse as main transcript	c.707C>T	p.Thr236Met	missense_variant, splice_region_variant	8/13	1	NM_001014436.3	P4	Q9UJU6-1

Frequencies

GnomAD3 genomes

AF:

0.00198

AC:

302

AN:

152224

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000434

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00445

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00248

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.0285

Gnomad NFE

AF:

0.00257

Gnomad OTH

AF:

0.00573

GnomAD3 exomes

AF:

0.00242

AC:

608

AN:

250778

Hom.:

AF XY:

0.00254

AC XY:

345

AN XY:

135748

show subpopulations

Gnomad AFR exome

AF:

0.000555

Gnomad AMR exome

AF:

0.00376

Gnomad ASJ exome

AF:

0.00219

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00147

Gnomad FIN exome

AF:

0.000278

Gnomad NFE exome

AF:

0.00314

Gnomad OTH exome

AF:

0.00654

GnomAD4 exome

AF:

0.00226

AC:

3307

AN:

1461856

Hom.:

Cov.:

AF XY:

0.00233

AC XY:

1693

AN XY:

727226

show subpopulations

Gnomad4 AFR exome

AF:

0.00116

Gnomad4 AMR exome

AF:

0.00418

Gnomad4 ASJ exome

AF:

0.00233

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.00151

Gnomad4 FIN exome

AF:

0.000206

Gnomad4 NFE exome

AF:

0.00235

Gnomad4 OTH exome

AF:

0.00293

GnomAD4 genome

AF:

0.00201

AC:

306

AN:

152342

Hom.:

Cov.:

AF XY:

0.00211

AC XY:

157

AN XY:

74502

show subpopulations

Gnomad4 AFR

AF:

0.000457

Gnomad4 AMR

AF:

0.00444

Gnomad4 ASJ

AF:

0.00202

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00269

Gnomad4 FIN

AF:

0.0000941

Gnomad4 NFE

AF:

0.00257

Gnomad4 OTH

AF:

0.00567

Alfa

AF:

0.00305

Hom.:

Bravo

AF:

0.00254

TwinsUK

AF:

0.00270

AC:

ALSPAC

AF:

0.00234

AC:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00244

AC:

ExAC

AF:

0.00245

AC:

297

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.00507

EpiControl

AF:

0.00474

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jul 01, 2022

DBNL: BP4 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.078

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.51

Cadd

Benign

Dann

Uncertain

1.0

DEOGEN2

Benign

0.054

T;.;.;.;T;.;.

Eigen

Benign

-0.19

Eigen_PC

Benign

-0.23

FATHMM_MKL

Benign

0.74

LIST_S2

Benign

0.51

T;T;T;T;T;T;T

M_CAP

Benign

0.029

MetaRNN

Benign

0.0039

T;T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.1

M;.;.;.;.;.;.

MutationTaster

Benign

0.97

N;N;N;N;N;N;N

PrimateAI

Benign

0.39

PROVEAN

Benign

-0.71

N;N;N;N;N;N;N

REVEL

Benign

0.067

Sift

Benign

0.077

T;T;T;T;T;T;T

Sift4G

Benign

0.10

T;T;T;T;T;T;T

Polyphen

0.97

D;.;.;.;D;D;D

Vest4

0.14

MVP

0.73

MPC

0.28

ClinPred

0.026

GERP RS

2.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.045

gMVP

0.11

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

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