Genetic Variant DNMBP:c.*10G>C (chr10-99877141-C-G) – ACMG Classification: Benign (-13 pts)

Variant summary

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

The NM_015221.4(DNMBP):c.*10G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00201 in 1,597,454 control chromosomes in the GnomAD database, including 57 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.010 ( 33 hom., cov: 32)

Exomes 𝑓: 0.0011 ( 24 hom. )

Consequence

DNMBP
NM_015221.4 3_prime_UTR

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.213

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:

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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=-0.78).

BP6

Variant 10-99877141-C-G is Benign according to our data. Variant chr10-99877141-C-G is described in ClinVar as [Benign]. Clinvar id is 3038451.Status of the report is no_assertion_criteria_provided, 0 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0102 (1554/152198) while in subpopulation AFR AF= 0.0352 (1460/41510). AF 95% confidence interval is 0.0337. There are 33 homozygotes in gnomad4. There are 741 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 33 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNMBP	NM_015221.4 link	c.*10G>C		3_prime_UTR_variant	Exon 17 of 17	ENST00000324109.9	NP_056036.1	Q6XZF7-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
DNMBP	ENST00000324109 link	c.*10G>C	3_prime_UTR_variant	Exon 17 of 17	1	NM_015221.4	ENSP00000315659.4	Q6XZF7-1
DNMBP	ENST00000543621 link	c.*10G>C	3_prime_UTR_variant	Exon 14 of 14	1		ENSP00000443657.2	A0A1C7CYY6
DNMBP	ENST00000636706 link	c.*10G>C	3_prime_UTR_variant	Exon 14 of 14	2		ENSP00000489875.1	A0A1B0GTX1

Frequencies

GnomAD3 genomes

AF:

0.0101

AC:

1541

AN:

152080

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0350

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00399

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.0101

GnomAD3 exomes

AF:

0.00272

AC:

634

AN:

232768

Hom.:

AF XY:

0.00201

AC XY:

253

AN XY:

125856

show subpopulations

Gnomad AFR exome

AF:

0.0345

Gnomad AMR exome

AF:

0.00236

Gnomad ASJ exome

AF:

0.000968

Gnomad EAS exome

AF:

0.0000600

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000177

Gnomad OTH exome

AF:

0.00127

GnomAD4 exome

AF:

0.00115

AC:

1661

AN:

1445256

Hom.:

Cov.:

AF XY:

0.00101

AC XY:

722

AN XY:

718064

show subpopulations

Gnomad4 AFR exome

AF:

0.0363

Gnomad4 AMR exome

AF:

0.00261

Gnomad4 ASJ exome

AF:

0.00102

Gnomad4 EAS exome

AF:

0.0000258

Gnomad4 SAS exome

AF:

0.0000240

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000179

Gnomad4 OTH exome

AF:

0.00214

GnomAD4 genome

AF:

0.0102

AC:

1554

AN:

152198

Hom.:

Cov.:

AF XY:

0.00996

AC XY:

741

AN XY:

74416

show subpopulations

Gnomad4 AFR

AF:

0.0352

Gnomad4 AMR

AF:

0.00399

Gnomad4 ASJ

AF:

0.00144

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000882

Gnomad4 OTH

AF:

0.00995

Alfa

AF:

0.00596

Hom.:

Bravo

AF:

0.0113

Asia WGS

AF:

0.00404

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

DNMBP-related disorder

Benign:1

Feb 18, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This 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

-0.78

CADD

Benign

3.3

DANN

Benign

0.48

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over