Variant 10-99929632-C-T 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.2261-20486G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0172 in 687,158 control chromosomes in the GnomAD database, including 187 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.013 ( 24 hom., cov: 32)

Exomes 𝑓: 0.018 ( 163 hom. )

Consequence

DNMBP
NM_015221.4 intron

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 2.13

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=0.0038205087).

BP6

Variant 10-99929632-C-T is Benign according to our data. Variant chr10-99929632-C-T is described in ClinVar as [Benign]. Clinvar id is 3041475.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.061 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNMBP	NM_015221.4 linkuse as main transcript	c.2261-20486G>A		intron_variant		ENST00000324109.9
DNMBP-AS1	NR_024130.3 linkuse as main transcript	n.176+1392C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNMBP	ENST00000324109.9 linkuse as main transcript	c.2261-20486G>A		intron_variant		1	NM_015221.4	P1	Q6XZF7-1
DNMBP-AS1	ENST00000661385.1 linkuse as main transcript	n.222+1392C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.0131

AC:

1993

AN:

152140

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00292

Gnomad AMI

AF:

0.0976

Gnomad AMR

AF:

0.0131

Gnomad ASJ

AF:

0.0357

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0352

Gnomad FIN

AF:

0.00358

Gnomad MID

AF:

0.0601

Gnomad NFE

AF:

0.0175

Gnomad OTH

AF:

0.0192

GnomAD3 exomes

AF:

0.0179

AC:

2136

AN:

119556

Hom.:

AF XY:

0.0195

AC XY:

1267

AN XY:

65066

show subpopulations

Gnomad AFR exome

AF:

0.00225

Gnomad AMR exome

AF:

0.0125

Gnomad ASJ exome

AF:

0.0320

Gnomad EAS exome

AF:

0.000304

Gnomad SAS exome

AF:

0.0332

Gnomad FIN exome

AF:

0.00446

Gnomad NFE exome

AF:

0.0181

Gnomad OTH exome

AF:

0.0285

GnomAD4 exome

AF:

0.0184

AC:

9846

AN:

534900

Hom.:

163

Cov.:

AF XY:

0.0195

AC XY:

5649

AN XY:

289778

show subpopulations

Gnomad4 AFR exome

AF:

0.00331

Gnomad4 AMR exome

AF:

0.0127

Gnomad4 ASJ exome

AF:

0.0304

Gnomad4 EAS exome

AF:

0.000219

Gnomad4 SAS exome

AF:

0.0334

Gnomad4 FIN exome

AF:

0.00406

Gnomad4 NFE exome

AF:

0.0185

Gnomad4 OTH exome

AF:

0.0222

GnomAD4 genome

AF:

0.0131

AC:

1989

AN:

152258

Hom.:

Cov.:

AF XY:

0.0124

AC XY:

922

AN XY:

74462

show subpopulations

Gnomad4 AFR

AF:

0.00291

Gnomad4 AMR

AF:

0.0131

Gnomad4 ASJ

AF:

0.0357

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0355

Gnomad4 FIN

AF:

0.00358

Gnomad4 NFE

AF:

0.0175

Gnomad4 OTH

AF:

0.0190

Alfa

AF:

0.0188

Hom.:

Bravo

AF:

0.0133

TwinsUK

AF:

0.0202

AC:

ALSPAC

AF:

0.0145

AC:

ExAC

AF:

0.0209

AC:

361

Asia WGS

AF:

0.0120

AC:

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

Sep 30, 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

-0.41

CADD

Benign

DANN

Benign

0.90

FATHMM_MKL

Benign

0.65

LIST_S2

Benign

0.54

MetaRNN

Benign

0.0038

MutationTaster

Benign

1.0

D;D;D

GERP RS

4.2

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