10-99930622-A-G

Variant names:

• chr10-99930622-A-G
• rs10883428
• NM_015221.4:c.2261-21476T>C

Variant summary

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

The NM_001318326.2(DNMBP):​c.142T>C​(p.Leu48Leu) variant causes a synonymous 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_001318326.2 synonymous
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 1.38

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 (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 rank	MANE	Protein	UniProt
DNMBP	NM_015221.4	c.2261-21476T>C		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.2261-21476T>C		intron_variant	Intron 4 of 16	1	NM_015221.4	ENSP00000315659.4

Frequencies

GnomAD3 genomes AF: 0.399 AC: 60550 AN: 151756 Hom.: 12248 Cov.: 31

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

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

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

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

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	-0.79
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

Other links and lift over

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