10-99879859-C-T

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.Pro1500=) 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

2

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]

Genome browser will be placed here

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/exons MANE Protein UniProt
DNMBPNM_015221.4 linkuse as main transcriptc.4500G>A p.Pro1500= synonymous_variant 16/17 ENST00000324109.9 NP_056036.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
DNMBPENST00000324109.9 linkuse as main transcriptc.4500G>A p.Pro1500= synonymous_variant 16/171 NM_015221.4 ENSP00000315659 P1Q6XZF7-1
DNMBPENST00000543621.6 linkuse as main transcriptc.2364G>A p.Pro788= synonymous_variant 13/141 ENSP00000443657
DNMBPENST00000636706.1 linkuse as main transcriptc.3396G>A p.Pro1132= synonymous_variant 13/142 ENSP00000489875

Frequencies

GnomAD3 genomes
AF:
0.00534
AC:
813
AN:
152222
Hom.:
24
Cov.:
32
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.:
90
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.:
31
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.:
23
Cov.:
32
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.:
3
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
Benign, no assertion criteria providedclinical testingPreventionGenetics, part of Exact SciencesApr 09, 2019This 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.

Other links and lift over

dbSNP: rs77307082; hg19: chr10-101639616; COSMIC: COSV60620544; API