Genetic Variant DNMBP:p.Pro1500Pro (chr10-99879859-C-T) – ACMG Classification: Benign (-14 pts)

Variant summary

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

The NM_015221.4(DNMBP):c.4500G>A(p.Pro1500Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00472 in 1,614,234 control chromosomes in the GnomAD database, including 195 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.0053 ( 23 hom., cov: 32)

Exomes 𝑓: 0.0047 ( 172 hom. )

Consequence

DNMBP
NM_015221.4 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.485

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=-0.74).

BP6

Variant 10-99879859-C-T is Benign according to our data. Variant chr10-99879859-C-T is described in ClinVar as [Benign]. Clinvar id is 3033669.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=0.485 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0741 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNMBP	NM_015221.4 link	c.4500G>A	p.Pro1500Pro	synonymous_variant	Exon 16 of 17	ENST00000324109.9	NP_056036.1	Q6XZF7-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
DNMBP	ENST00000324109.9 link	c.4500G>A	p.Pro1500Pro	synonymous_variant	Exon 16 of 17	1	NM_015221.4	ENSP00000315659.4	Q6XZF7-1
DNMBP	ENST00000543621.6 link	c.2364G>A	p.Pro788Pro	synonymous_variant	Exon 13 of 14	1		ENSP00000443657.2	A0A1C7CYY6
DNMBP	ENST00000636706.1 link	c.3396G>A	p.Pro1132Pro	synonymous_variant	Exon 13 of 14	2		ENSP00000489875.1	A0A1B0GTX1

Frequencies

GnomAD3 genomes

AF:

0.00534

AC:

813

AN:

152222

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000989

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00661

Gnomad ASJ

AF:

0.00374

Gnomad EAS

AF:

0.0809

Gnomad SAS

AF:

0.00269

Gnomad FIN

AF:

0.00650

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00219

Gnomad OTH

AF:

0.00335

GnomAD3 exomes

AF:

0.0116

AC:

2907

AN:

251072

Hom.:

AF XY:

0.00998

AC XY:

1354

AN XY:

135730

show subpopulations

Gnomad AFR exome

AF:

0.000492

Gnomad AMR exome

AF:

0.0220

Gnomad ASJ exome

AF:

0.00506

Gnomad EAS exome

AF:

0.0875

Gnomad SAS exome

AF:

0.00121

Gnomad FIN exome

AF:

0.00730

Gnomad NFE exome

AF:

0.00226

Gnomad OTH exome

AF:

0.00440

GnomAD4 exome

AF:

0.00465

AC:

6802

AN:

1461894

Hom.:

172

Cov.:

AF XY:

0.00447

AC XY:

3251

AN XY:

727248

show subpopulations

Gnomad4 AFR exome

AF:

0.000627

Gnomad4 AMR exome

AF:

0.0202

Gnomad4 ASJ exome

AF:

0.00459

Gnomad4 EAS exome

AF:

0.0811

Gnomad4 SAS exome

AF:

0.00179

Gnomad4 FIN exome

AF:

0.00730

Gnomad4 NFE exome

AF:

0.00150

Gnomad4 OTH exome

AF:

0.00530

GnomAD4 genome

AF:

0.00532

AC:

810

AN:

152340

Hom.:

Cov.:

AF XY:

0.00593

AC XY:

442

AN XY:

74486

show subpopulations

Gnomad4 AFR

AF:

0.000986

Gnomad4 AMR

AF:

0.00654

Gnomad4 ASJ

AF:

0.00374

Gnomad4 EAS

AF:

0.0805

Gnomad4 SAS

AF:

0.00290

Gnomad4 FIN

AF:

0.00650

Gnomad4 NFE

AF:

0.00219

Gnomad4 OTH

AF:

0.00331

Alfa

AF:

0.00294

Hom.:

Bravo

AF:

0.00601

Asia WGS

AF:

0.0330

AC:

113

AN:

3478

EpiCase

AF:

0.00147

EpiControl

AF:

0.000889

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

DNMBP-related disorder

Benign:1

Apr 09, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

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

-0.74

CADD

Benign

6.6

DANN

Benign

0.34

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