10-99930658-G-A

Variant names:

• chr10-99930658-G-A
• rs11190326
• NM_015221.4:c.2261-21512C>T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_001318326.2(DNMBP):​c.106C>T​(p.Leu36Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0397 in 702,888 control chromosomes in the GnomAD database, including 783 homozygotes. In-silico tool predicts a benign outcome for this variant. 7/8 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.047 (186 hom., cov: 32)
  • Exomes 𝑓: 0.038 (597 hom.)
• Consequence: DNMBP NM_001318326.2 missense
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: -0.0230

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)

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0020242035).
• BP6: Variant 10-99930658-G-A is Benign according to our data. Variant chr10-99930658-G-A is described in ClinVar as [Benign]. Clinvar id is 3059766.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0812 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNMBP	NM_015221.4	c.2261-21512C>T		intron_variant	Intron 4 of 16	ENST00000324109.9	NP_056036.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNMBP	ENST00000324109.9	c.2261-21512C>T		intron_variant	Intron 4 of 16	1	NM_015221.4	ENSP00000315659.4

Frequencies

GnomAD3 genomes AF: 0.0471 AC: 7164 AN: 152124 Hom.: 183 Cov.: 32

Gnomad AFR AF: 0.0835

Gnomad AMI AF: 0.0197

Gnomad AMR AF: 0.0333

Gnomad ASJ AF: 0.0216

Gnomad EAS AF: 0.0110

Gnomad SAS AF: 0.0822

Gnomad FIN AF: 0.0201

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0345

Gnomad OTH AF: 0.0411

GnomAD3 exomes AF: 0.0403 AC: 5415 AN: 134504 Hom.: 181 AF XY: 0.0438 AC XY: 3206 AN XY: 73254

Gnomad AFR exome AF: 0.0837

Gnomad AMR exome AF: 0.0186

Gnomad ASJ exome AF: 0.0220

Gnomad EAS exome AF: 0.0134

Gnomad SAS exome AF: 0.0867

Gnomad FIN exome AF: 0.0188

Gnomad NFE exome AF: 0.0364

Gnomad OTH exome AF: 0.0304

GnomAD4 exome AF: 0.0377 AC: 20745 AN: 550646 Hom.: 597 Cov.: 0 AF XY: 0.0405 AC XY: 12087 AN XY: 298102

Gnomad4 AFR exome AF: 0.0815

Gnomad4 AMR exome AF: 0.0195

Gnomad4 ASJ exome AF: 0.0215

Gnomad4 EAS exome AF: 0.00673

Gnomad4 SAS exome AF: 0.0831

Gnomad4 FIN exome AF: 0.0209

Gnomad4 NFE exome AF: 0.0346

Gnomad4 OTH exome AF: 0.0367

GnomAD4 genome AF: 0.0472 AC: 7181 AN: 152242 Hom.: 186 Cov.: 32 AF XY: 0.0473 AC XY: 3525 AN XY: 74454

Gnomad4 AFR AF: 0.0835

Gnomad4 AMR AF: 0.0332

Gnomad4 ASJ AF: 0.0216

Gnomad4 EAS AF: 0.0108

Gnomad4 SAS AF: 0.0819

Gnomad4 FIN AF: 0.0201

Gnomad4 NFE AF: 0.0345

Gnomad4 OTH AF: 0.0449

Alfa AF: 0.0426 Hom.: 30

Bravo AF: 0.0477

TwinsUK AF: 0.0326 AC: 121

ALSPAC AF: 0.0324 AC: 125

ExAC AF: 0.0470 AC: 837

Asia WGS AF: 0.0680 AC: 237 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

DNMBP-related disorder Benign:1

Apr 05, 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	-0.81
CADD	Benign	1.8
DANN	Benign	0.65
FATHMM_MKL	Benign	0.059	N
LIST_S2	Benign	0.34	T
MetaRNN	Benign	0.0020	T
GERP RS		0.70

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

Other links and lift over

dbSNP: rs11190326; hg19: chr10-101690415;