chr10-99930364-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_015221.4(DNMBP):​c.2261-21218G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0021 in 702,966 control chromosomes in the GnomAD database, including 14 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.0067 ( 12 hom., cov: 32)
Exomes 𝑓: 0.00081 ( 2 hom. )

Consequence

DNMBP
NM_015221.4 intron

Scores

6

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -1.67
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-AS1 (HGNC:20431): (DNMBP antisense RNA 1)

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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 (MetaRNN=0.0032663643).
BP6
Variant 10-99930364-C-T is Benign according to our data. Variant chr10-99930364-C-T is described in ClinVar as [Benign]. Clinvar id is 3042017.Status of the report is no_assertion_criteria_provided, 0 stars.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00674 (1026/152268) while in subpopulation AFR AF= 0.0235 (977/41536). AF 95% confidence interval is 0.0223. There are 12 homozygotes in gnomad4. There are 493 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 12 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
DNMBPNM_015221.4 linkuse as main transcriptc.2261-21218G>A intron_variant ENST00000324109.9 NP_056036.1
DNMBP-AS1NR_024130.3 linkuse as main transcriptn.176+2124C>T intron_variant, non_coding_transcript_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
DNMBPENST00000324109.9 linkuse as main transcriptc.2261-21218G>A intron_variant 1 NM_015221.4 ENSP00000315659 P1Q6XZF7-1
DNMBP-AS1ENST00000661385.1 linkuse as main transcriptn.222+2124C>T intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes
AF:
0.00673
AC:
1024
AN:
152150
Hom.:
12
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0235
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00203
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.0000942
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000103
Gnomad OTH
AF:
0.00478
GnomAD3 exomes
AF:
0.00132
AC:
178
AN:
134496
Hom.:
1
AF XY:
0.00115
AC XY:
84
AN XY:
73232
show subpopulations
Gnomad AFR exome
AF:
0.0244
Gnomad AMR exome
AF:
0.000736
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000445
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000379
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000812
AC:
447
AN:
550698
Hom.:
2
Cov.:
0
AF XY:
0.000641
AC XY:
191
AN XY:
298128
show subpopulations
Gnomad4 AFR exome
AF:
0.0223
Gnomad4 AMR exome
AF:
0.00101
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000478
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000221
Gnomad4 OTH exome
AF:
0.00157
GnomAD4 genome
AF:
0.00674
AC:
1026
AN:
152268
Hom.:
12
Cov.:
32
AF XY:
0.00662
AC XY:
493
AN XY:
74464
show subpopulations
Gnomad4 AFR
AF:
0.0235
Gnomad4 AMR
AF:
0.00203
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.0000942
Gnomad4 NFE
AF:
0.000103
Gnomad4 OTH
AF:
0.00473
Alfa
AF:
0.00235
Hom.:
0
Bravo
AF:
0.00727
ExAC
AF:
0.00119
AC:
20
Asia WGS
AF:
0.000577
AC:
2
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 providedclinical testingPreventionGenetics, part of Exact SciencesApr 11, 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
-0.83
CADD
Benign
0.28
DANN
Benign
0.55
FATHMM_MKL
Benign
0.024
N
LIST_S2
Benign
0.36
T
MetaRNN
Benign
0.0033
T
MutationTaster
Benign
1.0
N;N;N
GERP RS
-3.5

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: rs115073424; hg19: chr10-101690121; API