rs3740058

Positions:

• chr10-99896225-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015221.4(DNMBP):​c.3051+42C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.369 in 1,600,766 control chromosomes in the GnomAD database, including 112,054 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.32 (8203 hom., cov: 32)
  • Exomes 𝑓: 0.37 (103851 hom.)
• Consequence: DNMBP NM_015221.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.114

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.379 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNMBP	NM_015221.4	c.3051+42C>T		intron_variant		ENST00000324109.9	NP_056036.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNMBP	ENST00000324109.9	c.3051+42C>T		intron_variant		1	NM_015221.4	ENSP00000315659	P1
DNMBP	ENST00000543621.6	c.915+42C>T		intron_variant		1		ENSP00000443657
DNMBP	ENST00000636706.1	c.1947+42C>T		intron_variant		2		ENSP00000489875

Frequencies

GnomAD3 genomes AF: 0.316 AC: 48063 AN: 151946 Hom.: 8210 Cov.: 32

Gnomad AFR AF: 0.198

Gnomad AMI AF: 0.511

Gnomad AMR AF: 0.335

Gnomad ASJ AF: 0.344

Gnomad EAS AF: 0.210

Gnomad SAS AF: 0.344

Gnomad FIN AF: 0.337

Gnomad MID AF: 0.312

Gnomad NFE AF: 0.382

Gnomad OTH AF: 0.332

GnomAD3 exomes AF: 0.343 AC: 83245 AN: 242434 Hom.: 14514 AF XY: 0.349 AC XY: 45609 AN XY: 130848

Gnomad AFR exome AF: 0.196

Gnomad AMR exome AF: 0.342

Gnomad ASJ exome AF: 0.342

Gnomad EAS exome AF: 0.209

Gnomad SAS exome AF: 0.351

Gnomad FIN exome AF: 0.343

Gnomad NFE exome AF: 0.384

Gnomad OTH exome AF: 0.361

GnomAD4 exome AF: 0.375 AC: 543106 AN: 1448702 Hom.: 103851 Cov.: 30 AF XY: 0.375 AC XY: 269667 AN XY: 719568

Gnomad4 AFR exome AF: 0.191

Gnomad4 AMR exome AF: 0.342

Gnomad4 ASJ exome AF: 0.347

Gnomad4 EAS exome AF: 0.203

Gnomad4 SAS exome AF: 0.354

Gnomad4 FIN exome AF: 0.347

Gnomad4 NFE exome AF: 0.393

Gnomad4 OTH exome AF: 0.360

GnomAD4 genome AF: 0.316 AC: 48070 AN: 152064 Hom.: 8203 Cov.: 32 AF XY: 0.316 AC XY: 23467 AN XY: 74330

Gnomad4 AFR AF: 0.198

Gnomad4 AMR AF: 0.335

Gnomad4 ASJ AF: 0.344

Gnomad4 EAS AF: 0.209

Gnomad4 SAS AF: 0.344

Gnomad4 FIN AF: 0.337

Gnomad4 NFE AF: 0.382

Gnomad4 OTH AF: 0.331

Alfa AF: 0.354 Hom.: 3572

Bravo AF: 0.310

Asia WGS AF: 0.270 AC: 938 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	5.2
DANN	Benign	0.86

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: rs3740058; hg19: chr10-101655982; COSMIC: COSV60626159;