chr10-99877160-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BS1BS2

The NM_015221.4(DNMBP):​c.4725G>A​(p.Glu1575=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0225 in 1,609,802 control chromosomes in the GnomAD database, including 435 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.017 ( 23 hom., cov: 32)
Exomes 𝑓: 0.023 ( 412 hom. )

Consequence

DNMBP
NM_015221.4 synonymous

Scores

2

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.350
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]

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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=-0.48).
BP6
Variant 10-99877160-C-T is Benign according to our data. Variant chr10-99877160-C-T is described in ClinVar as [Benign]. Clinvar id is 3038273.Status of the report is no_assertion_criteria_provided, 0 stars.
BP7
Synonymous conserved (PhyloP=0.35 with no splicing effect.
BS1
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0172 (2620/152240) while in subpopulation NFE AF= 0.0248 (1685/68020). AF 95% confidence interval is 0.0238. There are 23 homozygotes in gnomad4. There are 1258 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 23 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
DNMBPNM_015221.4 linkuse as main transcriptc.4725G>A p.Glu1575= synonymous_variant 17/17 ENST00000324109.9 NP_056036.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
DNMBPENST00000324109.9 linkuse as main transcriptc.4725G>A p.Glu1575= synonymous_variant 17/171 NM_015221.4 ENSP00000315659 P1Q6XZF7-1
DNMBPENST00000543621.6 linkuse as main transcriptc.2589G>A p.Glu863= synonymous_variant 14/141 ENSP00000443657
DNMBPENST00000636706.1 linkuse as main transcriptc.3621G>A p.Glu1207= synonymous_variant 14/142 ENSP00000489875

Frequencies

GnomAD3 genomes
AF:
0.0172
AC:
2623
AN:
152122
Hom.:
23
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00418
Gnomad AMI
AF:
0.0482
Gnomad AMR
AF:
0.0136
Gnomad ASJ
AF:
0.0245
Gnomad EAS
AF:
0.000193
Gnomad SAS
AF:
0.0104
Gnomad FIN
AF:
0.0329
Gnomad MID
AF:
0.0127
Gnomad NFE
AF:
0.0248
Gnomad OTH
AF:
0.0110
GnomAD3 exomes
AF:
0.0185
AC:
4529
AN:
245038
Hom.:
68
AF XY:
0.0185
AC XY:
2447
AN XY:
132466
show subpopulations
Gnomad AFR exome
AF:
0.00395
Gnomad AMR exome
AF:
0.00654
Gnomad ASJ exome
AF:
0.0292
Gnomad EAS exome
AF:
0.0000563
Gnomad SAS exome
AF:
0.00973
Gnomad FIN exome
AF:
0.0323
Gnomad NFE exome
AF:
0.0255
Gnomad OTH exome
AF:
0.0207
GnomAD4 exome
AF:
0.0231
AC:
33664
AN:
1457562
Hom.:
412
Cov.:
31
AF XY:
0.0227
AC XY:
16446
AN XY:
724952
show subpopulations
Gnomad4 AFR exome
AF:
0.00354
Gnomad4 AMR exome
AF:
0.00760
Gnomad4 ASJ exome
AF:
0.0270
Gnomad4 EAS exome
AF:
0.0000254
Gnomad4 SAS exome
AF:
0.00939
Gnomad4 FIN exome
AF:
0.0341
Gnomad4 NFE exome
AF:
0.0258
Gnomad4 OTH exome
AF:
0.0188
GnomAD4 genome
AF:
0.0172
AC:
2620
AN:
152240
Hom.:
23
Cov.:
32
AF XY:
0.0169
AC XY:
1258
AN XY:
74432
show subpopulations
Gnomad4 AFR
AF:
0.00416
Gnomad4 AMR
AF:
0.0136
Gnomad4 ASJ
AF:
0.0245
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.00996
Gnomad4 FIN
AF:
0.0329
Gnomad4 NFE
AF:
0.0248
Gnomad4 OTH
AF:
0.0109
Alfa
AF:
0.0222
Hom.:
13
Bravo
AF:
0.0154
Asia WGS
AF:
0.00433
AC:
15
AN:
3478
EpiCase
AF:
0.0236
EpiControl
AF:
0.0235

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 SciencesFeb 21, 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
-0.48
CADD
Benign
8.2
DANN
Benign
0.40

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: rs11190304; hg19: chr10-101636917; API