Genetic Variant NM_001363541.2:c.1718G>T (chr5-177458254-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001363541.2(DBN1):c.1718G>T(p.Cys573Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,418 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

DBN1
NM_001363541.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.32

Publications

0 publications found

Variant links:

Genes affected

DBN1 (HGNC:2695): (drebrin 1) The protein encoded by this gene is a cytoplasmic actin-binding protein thought to play a role in the process of neuronal growth. It is a member of the drebrin family of proteins that are developmentally regulated in the brain. A decrease in the amount of this protein in the brain has been implicated as a possible contributing factor in the pathogenesis of memory disturbance in Alzheimer's disease. At least two alternative splice variants encoding different protein isoforms have been described for this gene. [provided by RefSeq, Jul 2008]

DBN1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.1580801).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001363541.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DBN1	NM_001363541.2	MANE Select	c.1718G>T	p.Cys573Phe	missense	Exon 13 of 15	NP_001350470.2	Q16643-3
DBN1	NM_001393630.1		c.1724G>T	p.Cys575Phe	missense	Exon 14 of 16	NP_001380559.1
DBN1	NM_001364151.2		c.1715G>T	p.Cys572Phe	missense	Exon 13 of 15	NP_001351080.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DBN1	ENST00000393565.6	TSL:5 MANE Select	c.1718G>T	p.Cys573Phe	missense	Exon 13 of 15	ENSP00000377195.1	Q16643-3
DBN1	ENST00000292385.9	TSL:1	c.1586G>T	p.Cys529Phe	missense	Exon 13 of 15	ENSP00000292385.5	Q16643-2
DBN1	ENST00000309007.9	TSL:1	c.1580G>T	p.Cys527Phe	missense	Exon 12 of 14	ENSP00000308532.5	Q16643-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000201

AC:

AN:

249078

AF XY:

0.00000741

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000145

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000342

AC:

AN:

1461418

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726990

show subpopulations

African (AFR)

AF:

0.0000299

AC:

AN:

33480

American (AMR)

AF:

0.0000895

AC:

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26130

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.00

AC:

AN:

86256

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53064

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111918

Other (OTH)

AF:

0.00

AC:

AN:

60388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.445

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ExAC

AF:

0.00000824

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.084

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.42

CADD

Benign

(source)

DANN

Benign

0.94

DEOGEN2

Benign

0.14

Eigen

Benign

-0.19

Eigen_PC

Benign

-0.079

FATHMM_MKL

Uncertain

0.84

LIST_S2

Benign

0.81

M_CAP

Benign

0.018

MetaRNN

Benign

0.16

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.90

PhyloP100

2.3

PrimateAI

Benign

0.46

PROVEAN

Benign

-0.99

REVEL

Benign

0.048

Sift

Uncertain

0.010

Sift4G

Benign

0.70

Polyphen

0.10

Vest4

0.29

MutPred

0.26

Gain of sheet (P = 0.0266)

MVP

0.24

MPC

0.36

ClinPred

0.20

GERP RS

4.6

Varity_R

0.46

gMVP

0.054

Mutation Taster

=84/16

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over