Variant chr10-99930622-A-G 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.2261-21476T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.378 in 702,500 control chromosomes in the GnomAD database, including 51,166 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.40 ( 12257 hom., cov: 31)

Exomes 𝑓: 0.37 ( 38909 hom. )

Consequence

DNMBP
NM_015221.4 intron

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 1.38

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant 10-99930622-A-G is Benign according to our data. Variant chr10-99930622-A-G is described in ClinVar as [Benign]. Clinvar id is 3059290.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.467 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.2261-21476T>C		intron_variant		ENST00000324109.9	NP_056036.1
DNMBP-AS1	NR_024130.3 linkuse as main transcript	n.176+2382A>G		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.2261-21476T>C		intron_variant		1	NM_015221.4	ENSP00000315659	P1	Q6XZF7-1
DNMBP-AS1	ENST00000661385.1 linkuse as main transcript	n.222+2382A>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.399

AC:

60550

AN:

151756

Hom.:

12248

Cov.:

show subpopulations

Gnomad AFR

AF:

0.472

Gnomad AMI

AF:

0.506

Gnomad AMR

AF:

0.394

Gnomad ASJ

AF:

0.358

Gnomad EAS

AF:

0.251

Gnomad SAS

AF:

0.344

Gnomad FIN

AF:

0.324

Gnomad MID

AF:

0.399

Gnomad NFE

AF:

0.383

Gnomad OTH

AF:

0.397

GnomAD3 exomes

AF:

0.373

AC:

50228

AN:

134488

Hom.:

9602

AF XY:

0.369

AC XY:

27043

AN XY:

73226

show subpopulations

Gnomad AFR exome

AF:

0.478

Gnomad AMR exome

AF:

0.419

Gnomad ASJ exome

AF:

0.352

Gnomad EAS exome

AF:

0.252

Gnomad SAS exome

AF:

0.340

Gnomad FIN exome

AF:

0.333

Gnomad NFE exome

AF:

0.384

Gnomad OTH exome

AF:

0.397

GnomAD4 exome

AF:

0.373

AC:

205276

AN:

550626

Hom.:

38909

Cov.:

AF XY:

0.370

AC XY:

110418

AN XY:

298084

show subpopulations

Gnomad4 AFR exome

AF:

0.479

Gnomad4 AMR exome

AF:

0.414

Gnomad4 ASJ exome

AF:

0.355

Gnomad4 EAS exome

AF:

0.249

Gnomad4 SAS exome

AF:

0.342

Gnomad4 FIN exome

AF:

0.335

Gnomad4 NFE exome

AF:

0.386

Gnomad4 OTH exome

AF:

0.382

GnomAD4 genome

AF:

0.399

AC:

60605

AN:

151874

Hom.:

12257

Cov.:

AF XY:

0.396

AC XY:

29377

AN XY:

74246

show subpopulations

Gnomad4 AFR

AF:

0.472

Gnomad4 AMR

AF:

0.394

Gnomad4 ASJ

AF:

0.358

Gnomad4 EAS

AF:

0.250

Gnomad4 SAS

AF:

0.343

Gnomad4 FIN

AF:

0.324

Gnomad4 NFE

AF:

0.383

Gnomad4 OTH

AF:

0.398

Alfa

AF:

0.390

Hom.:

16679

Bravo

AF:

0.408

Asia WGS

AF:

0.301

AC:

1043

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

Feb 18, 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

-0.79

CADD

Benign

DANN

Benign

0.63

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