dbSNP rs2255901: DNMBP:p.Ser1440Ser (chr10-99880039-G-A) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_015221.4(DNMBP):c.4320C>T(p.Ser1440Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.509 in 1,613,852 control chromosomes in the GnomAD database, including 211,787 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.50 ( 19745 hom., cov: 32)

Exomes 𝑓: 0.51 ( 192042 hom. )

Consequence

DNMBP
NM_015221.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.845

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 10-99880039-G-A is Benign according to our data. Variant chr10-99880039-G-A is described in ClinVar as [Benign]. Clinvar id is 1255519.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.534 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNMBP	NM_015221.4 link	c.4320C>T	p.Ser1440Ser	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.4320C>T	p.Ser1440Ser	synonymous_variant	Exon 16 of 17	1	NM_015221.4	ENSP00000315659.4	Q6XZF7-1
DNMBP	ENST00000543621.6 link	c.2184C>T	p.Ser728Ser	synonymous_variant	Exon 13 of 14	1		ENSP00000443657.2	A0A1C7CYY6
DNMBP	ENST00000636706.1 link	c.3216C>T	p.Ser1072Ser	synonymous_variant	Exon 13 of 14	2		ENSP00000489875.1	A0A1B0GTX1

Frequencies

GnomAD3 genomes

AF:

0.505

AC:

76657

AN:

151900

Hom.:

19712

Cov.:

show subpopulations

Gnomad AFR

AF:

0.539

Gnomad AMI

AF:

0.569

Gnomad AMR

AF:

0.507

Gnomad ASJ

AF:

0.490

Gnomad EAS

AF:

0.255

Gnomad SAS

AF:

0.489

Gnomad FIN

AF:

0.419

Gnomad MID

AF:

0.601

Gnomad NFE

AF:

0.515

Gnomad OTH

AF:

0.535

GnomAD3 exomes

AF:

0.484

AC:

121671

AN:

251458

Hom.:

30185

AF XY:

0.487

AC XY:

66238

AN XY:

135908

show subpopulations

Gnomad AFR exome

AF:

0.543

Gnomad AMR exome

AF:

0.478

Gnomad ASJ exome

AF:

0.488

Gnomad EAS exome

AF:

0.258

Gnomad SAS exome

AF:

0.497

Gnomad FIN exome

AF:

0.424

Gnomad NFE exome

AF:

0.520

Gnomad OTH exome

AF:

0.509

GnomAD4 exome

AF:

0.509

AC:

744586

AN:

1461834

Hom.:

192042

Cov.:

AF XY:

0.510

AC XY:

370684

AN XY:

727218

show subpopulations

Gnomad4 AFR exome

AF:

0.547

Gnomad4 AMR exome

AF:

0.479

Gnomad4 ASJ exome

AF:

0.497

Gnomad4 EAS exome

AF:

0.257

Gnomad4 SAS exome

AF:

0.496

Gnomad4 FIN exome

AF:

0.428

Gnomad4 NFE exome

AF:

0.524

Gnomad4 OTH exome

AF:

0.504

GnomAD4 genome

AF:

0.505

AC:

76746

AN:

152018

Hom.:

19745

Cov.:

AF XY:

0.501

AC XY:

37216

AN XY:

74294

show subpopulations

Gnomad4 AFR

AF:

0.540

Gnomad4 AMR

AF:

0.507

Gnomad4 ASJ

AF:

0.490

Gnomad4 EAS

AF:

0.254

Gnomad4 SAS

AF:

0.489

Gnomad4 FIN

AF:

0.419

Gnomad4 NFE

AF:

0.515

Gnomad4 OTH

AF:

0.538

Alfa

AF:

0.515

Hom.:

10669

Bravo

AF:

0.514

Asia WGS

AF:

0.411

AC:

1429

AN:

3478

EpiCase

AF:

0.529

EpiControl

AF:

0.541

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

DNMBP-related disorder

Benign:1

Oct 21, 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). -

Cataract 48

Benign:1

Jul 30, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

0.51

DANN

Benign

0.41

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