Variant 10-99929621-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_001318326.2(DNMBP):c.1143C>G(p.Ser381Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.498 in 676,142 control chromosomes in the GnomAD database, including 86,529 homozygotes. In-silico tool predicts a benign outcome for this variant. 7/8 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.53 ( 21667 hom., cov: 31)

Exomes 𝑓: 0.49 ( 64862 hom. )

Consequence

DNMBP
NM_001318326.2 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.639

Variant links:

Genes affected

DNMBP (HGNC:30373): (dynamin binding protein) This gene encodes a protein belonging to the guanine nucleotide exchange factor family, and which regulates the configuration of cell junctions. It contains multiple binding sites for dynamin and thus links dynamin to actin regulatory proteins. Polymorphisms in this gene have been linked to Alzheimer's disease in some populations, though there are conflicting reports of such linkages in other populations. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2015]

DNMBP links:

DNMBP-AS1 (HGNC:):

DNMBP-AS1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.6306592E-5).

BP6

Variant 10-99929621-G-C is Benign according to our data. Variant chr10-99929621-G-C is described in ClinVar as [Benign]. Clinvar id is 3059416.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.615 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNMBP	NM_015221.4 linkuse as main transcript	c.2261-20475C>G		intron_variant		ENST00000324109.9	NP_056036.1	Q6XZF7-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNMBP	ENST00000324109.9 linkuse as main transcript	c.2261-20475C>G		intron_variant		1	NM_015221.4	ENSP00000315659.4		Q6XZF7-1

Frequencies

GnomAD3 genomes

AF:

0.526

AC:

79845

AN:

151882

Hom.:

21638

Cov.:

show subpopulations

Gnomad AFR

AF:

0.621

Gnomad AMI

AF:

0.547

Gnomad AMR

AF:

0.509

Gnomad ASJ

AF:

0.509

Gnomad EAS

AF:

0.244

Gnomad SAS

AF:

0.482

Gnomad FIN

AF:

0.413

Gnomad MID

AF:

0.646

Gnomad NFE

AF:

0.513

Gnomad OTH

AF:

0.553

GnomAD3 exomes

AF:

0.486

AC:

54173

AN:

111494

Hom.:

13689

AF XY:

0.487

AC XY:

29617

AN XY:

60816

show subpopulations

Gnomad AFR exome

AF:

0.626

Gnomad AMR exome

AF:

0.489

Gnomad ASJ exome

AF:

0.500

Gnomad EAS exome

AF:

0.238

Gnomad SAS exome

AF:

0.489

Gnomad FIN exome

AF:

0.422

Gnomad NFE exome

AF:

0.518

Gnomad OTH exome

AF:

0.519

GnomAD4 exome

AF:

0.490

AC:

256630

AN:

524142

Hom.:

64862

Cov.:

AF XY:

0.490

AC XY:

139134

AN XY:

283838

show subpopulations

Gnomad4 AFR exome

AF:

0.621

Gnomad4 AMR exome

AF:

0.485

Gnomad4 ASJ exome

AF:

0.511

Gnomad4 EAS exome

AF:

0.232

Gnomad4 SAS exome

AF:

0.486

Gnomad4 FIN exome

AF:

0.424

Gnomad4 NFE exome

AF:

0.515

Gnomad4 OTH exome

AF:

0.507

GnomAD4 genome

AF:

0.526

AC:

79935

AN:

152000

Hom.:

21667

Cov.:

AF XY:

0.520

AC XY:

38641

AN XY:

74296

show subpopulations

Gnomad4 AFR

AF:

0.622

Gnomad4 AMR

AF:

0.509

Gnomad4 ASJ

AF:

0.509

Gnomad4 EAS

AF:

0.244

Gnomad4 SAS

AF:

0.481

Gnomad4 FIN

AF:

0.413

Gnomad4 NFE

AF:

0.513

Gnomad4 OTH

AF:

0.557

Alfa

AF:

0.435

Hom.:

2080

Bravo

AF:

0.537

TwinsUK

AF:

0.534

AC:

1979

ALSPAC

AF:

0.511

AC:

1969

ExAC

AF:

0.434

AC:

6813

Asia WGS

AF:

0.401

AC:

1393

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

DNMBP-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 18, 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

-0.43

CADD

Benign

DANN

Benign

0.92

FATHMM_MKL

Benign

0.059

LIST_S2

Benign

0.24

MetaRNN

Benign

0.000016

GERP RS

4.1

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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