dbSNP rs3740058: DNMBP:c.3051+42C>T (chr10-99896225-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_015221.4(DNMBP):c.3051+42C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.369 in 1,600,766 control chromosomes in the GnomAD database, including 112,054 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.32 ( 8203 hom., cov: 32)

Exomes 𝑓: 0.37 ( 103851 hom. )

Consequence

DNMBP
NM_015221.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.114

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 was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.65).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.379 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNMBP	NM_015221.4 link	c.3051+42C>T		intron_variant	Intron 10 of 16	ENST00000324109.9	NP_056036.1	Q6XZF7-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
DNMBP	ENST00000324109.9 link	c.3051+42C>T	intron_variant	Intron 10 of 16	1	NM_015221.4	ENSP00000315659.4	Q6XZF7-1
DNMBP	ENST00000543621.6 link	c.915+42C>T	intron_variant	Intron 7 of 13	1		ENSP00000443657.2	A0A1C7CYY6
DNMBP	ENST00000636706.1 link	c.1947+42C>T	intron_variant	Intron 7 of 13	2		ENSP00000489875.1	A0A1B0GTX1

Frequencies

GnomAD3 genomes

AF:

0.316

AC:

48063

AN:

151946

Hom.:

8210

Cov.:

show subpopulations

Gnomad AFR

AF:

0.198

Gnomad AMI

AF:

0.511

Gnomad AMR

AF:

0.335

Gnomad ASJ

AF:

0.344

Gnomad EAS

AF:

0.210

Gnomad SAS

AF:

0.344

Gnomad FIN

AF:

0.337

Gnomad MID

AF:

0.312

Gnomad NFE

AF:

0.382

Gnomad OTH

AF:

0.332

GnomAD2 exomes

AF:

0.343

AC:

83245

AN:

242434

AF XY:

0.349

show subpopulations

Gnomad AFR exome

AF:

0.196

Gnomad AMR exome

AF:

0.342

Gnomad ASJ exome

AF:

0.342

Gnomad EAS exome

AF:

0.209

Gnomad FIN exome

AF:

0.343

Gnomad NFE exome

AF:

0.384

Gnomad OTH exome

AF:

0.361

GnomAD4 exome

AF:

0.375

AC:

543106

AN:

1448702

Hom.:

103851

Cov.:

AF XY:

0.375

AC XY:

269667

AN XY:

719568

show subpopulations

Gnomad4 AFR exome

AF:

0.191

AC:

6333

AN:

33224

Gnomad4 AMR exome

AF:

0.342

AC:

15032

AN:

43932

Gnomad4 ASJ exome

AF:

0.347

AC:

8926

AN:

25724

Gnomad4 EAS exome

AF:

0.203

AC:

7984

AN:

39422

Gnomad4 SAS exome

AF:

0.354

AC:

30134

AN:

85088

Gnomad4 FIN exome

AF:

0.347

AC:

18385

AN:

53012

Gnomad4 NFE exome

AF:

0.393

AC:

433148

AN:

1102758

Gnomad4 Remaining exome

AF:

0.360

AC:

21512

AN:

59828

Heterozygous variant carriers

14188

28377

42565

56754

70942

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

13476

26952

40428

53904

67380

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.316

AC:

48070

AN:

152064

Hom.:

8203

Cov.:

AF XY:

0.316

AC XY:

23467

AN XY:

74330

show subpopulations

Gnomad4 AFR

AF:

0.198

AC:

0.197995

AN:

0.197995

Gnomad4 AMR

AF:

0.335

AC:

0.334686

AN:

0.334686

Gnomad4 ASJ

AF:

0.344

AC:

0.34438

AN:

0.34438

Gnomad4 EAS

AF:

0.209

AC:

0.209123

AN:

0.209123

Gnomad4 SAS

AF:

0.344

AC:

0.343763

AN:

0.343763

Gnomad4 FIN

AF:

0.337

AC:

0.337441

AN:

0.337441

Gnomad4 NFE

AF:

0.382

AC:

0.382434

AN:

0.382434

Gnomad4 OTH

AF:

0.331

AC:

0.331439

AN:

0.331439

Heterozygous variant carriers

1643

3285

4928

6570

8213

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Genome Hom

Variant carriers

484

968

1452

1936

2420

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.351

Hom.:

4268

Bravo

AF:

0.310

Asia WGS

AF:

0.270

AC:

938

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.65

CADD

Benign

5.2

DANN

Benign

0.86

Mutation Taster

=100/0

polymorphism (auto)

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over