10-99930622-A-G

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

2

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-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 (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
DNMBPNM_015221.4 linkuse as main transcriptc.2261-21476T>C intron_variant ENST00000324109.9 NP_056036.1
DNMBP-AS1NR_024130.3 linkuse as main transcriptn.176+2382A>G 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.2261-21476T>C intron_variant 1 NM_015221.4 ENSP00000315659 P1Q6XZF7-1
DNMBP-AS1ENST00000661385.1 linkuse as main transcriptn.222+2382A>G intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes
AF:
0.399
AC:
60550
AN:
151756
Hom.:
12248
Cov.:
31
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.:
0
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.:
31
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 providedclinical testingPreventionGenetics, part of Exact SciencesFeb 18, 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
-0.79
CADD
Benign
13
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.

Other links and lift over

dbSNP: rs10883428; hg19: chr10-101690379; COSMIC: COSV60625436; COSMIC: COSV60625436; API