Variant 10-99879925-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BA1

The NM_015221.4(DNMBP):c.4434C>T(p.Ser1478=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0363 in 1,614,182 control chromosomes in the GnomAD database, including 1,351 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.032 ( 82 hom., cov: 32)

Exomes 𝑓: 0.037 ( 1269 hom. )

Consequence

DNMBP
NM_015221.4 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -1.50

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:

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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=-0.73).

BP6

Variant 10-99879925-G-A is Benign according to our data. Variant chr10-99879925-G-A is described in ClinVar as [Benign]. Clinvar id is 3060443.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=-1.5 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0814 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.4434C>T	p.Ser1478=	synonymous_variant	16/17	ENST00000324109.9	NP_056036.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNMBP	ENST00000324109.9 linkuse as main transcript	c.4434C>T	p.Ser1478=	synonymous_variant	16/17	1	NM_015221.4	ENSP00000315659	P1	Q6XZF7-1
DNMBP	ENST00000543621.6 linkuse as main transcript	c.2298C>T	p.Ser766=	synonymous_variant	13/14	1		ENSP00000443657
DNMBP	ENST00000636706.1 linkuse as main transcript	c.3330C>T	p.Ser1110=	synonymous_variant	13/14	2		ENSP00000489875

Frequencies

GnomAD3 genomes

AF:

0.0317

AC:

4831

AN:

152170

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0270

Gnomad AMI

AF:

0.0197

Gnomad AMR

AF:

0.0280

Gnomad ASJ

AF:

0.0236

Gnomad EAS

AF:

0.00154

Gnomad SAS

AF:

0.0878

Gnomad FIN

AF:

0.0244

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.0357

Gnomad OTH

AF:

0.0287

GnomAD3 exomes

AF:

0.0354

AC:

8892

AN:

251482

Hom.:

258

AF XY:

0.0390

AC XY:

5302

AN XY:

135914

show subpopulations

Gnomad AFR exome

AF:

0.0282

Gnomad AMR exome

AF:

0.0157

Gnomad ASJ exome

AF:

0.0221

Gnomad EAS exome

AF:

0.000870

Gnomad SAS exome

AF:

0.0921

Gnomad FIN exome

AF:

0.0277

Gnomad NFE exome

AF:

0.0355

Gnomad OTH exome

AF:

0.0314

GnomAD4 exome

AF:

0.0368

AC:

53824

AN:

1461894

Hom.:

1269

Cov.:

AF XY:

0.0385

AC XY:

27978

AN XY:

727248

show subpopulations

Gnomad4 AFR exome

AF:

0.0259

Gnomad4 AMR exome

AF:

0.0163

Gnomad4 ASJ exome

AF:

0.0236

Gnomad4 EAS exome

AF:

0.000655

Gnomad4 SAS exome

AF:

0.0885

Gnomad4 FIN exome

AF:

0.0265

Gnomad4 NFE exome

AF:

0.0362

Gnomad4 OTH exome

AF:

0.0356

GnomAD4 genome

AF:

0.0318

AC:

4844

AN:

152288

Hom.:

Cov.:

AF XY:

0.0317

AC XY:

2360

AN XY:

74472

show subpopulations

Gnomad4 AFR

AF:

0.0270

Gnomad4 AMR

AF:

0.0279

Gnomad4 ASJ

AF:

0.0236

Gnomad4 EAS

AF:

0.00154

Gnomad4 SAS

AF:

0.0883

Gnomad4 FIN

AF:

0.0244

Gnomad4 NFE

AF:

0.0358

Gnomad4 OTH

AF:

0.0326

Alfa

AF:

0.0329

Hom.:

Bravo

AF:

0.0296

Asia WGS

AF:

0.0660

AC:

230

AN:

3478

EpiCase

AF:

0.0364

EpiControl

AF:

0.0361

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

Apr 05, 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

-0.73

CADD

Benign

1.6

DANN

Benign

0.49

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