Variant 10-99930658-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_015221.4(DNMBP):c.2261-21512C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0397 in 702,888 control chromosomes in the GnomAD database, including 783 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.047 ( 186 hom., cov: 32)

Exomes 𝑓: 0.038 ( 597 hom. )

Consequence

DNMBP
NM_015221.4 intron

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.0230

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:20431): (DNMBP antisense RNA 1)

DNMBP-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0020242035).

BP6

Variant 10-99930658-G-A is Benign according to our data. Variant chr10-99930658-G-A is described in ClinVar as [Benign]. Clinvar id is 3059766.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0812 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.2261-21512C>T		intron_variant		ENST00000324109.9	NP_056036.1
DNMBP-AS1	NR_024130.3 linkuse as main transcript	n.176+2418G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNMBP	ENST00000324109.9 linkuse as main transcript	c.2261-21512C>T		intron_variant		1	NM_015221.4	ENSP00000315659	P1	Q6XZF7-1
DNMBP-AS1	ENST00000661385.1 linkuse as main transcript	n.222+2418G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.0471

AC:

7164

AN:

152124

Hom.:

183

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0835

Gnomad AMI

AF:

0.0197

Gnomad AMR

AF:

0.0333

Gnomad ASJ

AF:

0.0216

Gnomad EAS

AF:

0.0110

Gnomad SAS

AF:

0.0822

Gnomad FIN

AF:

0.0201

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.0345

Gnomad OTH

AF:

0.0411

GnomAD3 exomes

AF:

0.0403

AC:

5415

AN:

134504

Hom.:

181

AF XY:

0.0438

AC XY:

3206

AN XY:

73254

show subpopulations

Gnomad AFR exome

AF:

0.0837

Gnomad AMR exome

AF:

0.0186

Gnomad ASJ exome

AF:

0.0220

Gnomad EAS exome

AF:

0.0134

Gnomad SAS exome

AF:

0.0867

Gnomad FIN exome

AF:

0.0188

Gnomad NFE exome

AF:

0.0364

Gnomad OTH exome

AF:

0.0304

GnomAD4 exome

AF:

0.0377

AC:

20745

AN:

550646

Hom.:

597

Cov.:

AF XY:

0.0405

AC XY:

12087

AN XY:

298102

show subpopulations

Gnomad4 AFR exome

AF:

0.0815

Gnomad4 AMR exome

AF:

0.0195

Gnomad4 ASJ exome

AF:

0.0215

Gnomad4 EAS exome

AF:

0.00673

Gnomad4 SAS exome

AF:

0.0831

Gnomad4 FIN exome

AF:

0.0209

Gnomad4 NFE exome

AF:

0.0346

Gnomad4 OTH exome

AF:

0.0367

GnomAD4 genome

AF:

0.0472

AC:

7181

AN:

152242

Hom.:

186

Cov.:

AF XY:

0.0473

AC XY:

3525

AN XY:

74454

show subpopulations

Gnomad4 AFR

AF:

0.0835

Gnomad4 AMR

AF:

0.0332

Gnomad4 ASJ

AF:

0.0216

Gnomad4 EAS

AF:

0.0108

Gnomad4 SAS

AF:

0.0819

Gnomad4 FIN

AF:

0.0201

Gnomad4 NFE

AF:

0.0345

Gnomad4 OTH

AF:

0.0449

Alfa

AF:

0.0426

Hom.:

Bravo

AF:

0.0477

TwinsUK

AF:

0.0326

AC:

121

ALSPAC

AF:

0.0324

AC:

125

ExAC

AF:

0.0470

AC:

837

Asia WGS

AF:

0.0680

AC:

237

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

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

-0.81

CADD

Benign

1.8

DANN

Benign

0.65

FATHMM_MKL

Benign

0.059

LIST_S2

Benign

0.34

MetaRNN

Benign

0.0020

MutationTaster

Benign

1.0

P;P;P

GERP RS

0.70

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