rs3740057

Positions:

• chr10-99898828-T-C

Variant summary

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

The NM_015221.4(DNMBP):​c.2703-68A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.447 in 1,399,874 control chromosomes in the GnomAD database, including 142,900 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 0.44 (15184 hom., cov: 33)
  • Exomes 𝑓: 0.45 (127716 hom.)
• Consequence: DNMBP NM_015221.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.71

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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.455 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNMBP	NM_015221.4	c.2703-68A>G		intron_variant		ENST00000324109.9	NP_056036.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNMBP	ENST00000324109.9	c.2703-68A>G		intron_variant		1	NM_015221.4	ENSP00000315659.4
DNMBP	ENST00000543621.6	c.567-68A>G		intron_variant		1		ENSP00000443657.2
DNMBP	ENST00000636706.1	c.1599-68A>G		intron_variant		2		ENSP00000489875.1

Frequencies

GnomAD3 genomes AF: 0.443 AC: 67379 AN: 151970 Hom.: 15177 Cov.: 33

Gnomad AFR AF: 0.460

Gnomad AMI AF: 0.542

Gnomad AMR AF: 0.434

Gnomad ASJ AF: 0.409

Gnomad EAS AF: 0.233

Gnomad SAS AF: 0.455

Gnomad FIN AF: 0.396

Gnomad MID AF: 0.385

Gnomad NFE AF: 0.458

Gnomad OTH AF: 0.449

GnomAD4 exome AF: 0.448 AC: 558980 AN: 1247786 Hom.: 127716 AF XY: 0.450 AC XY: 283789 AN XY: 631248

Gnomad4 AFR exome AF: 0.464

Gnomad4 AMR exome AF: 0.431

Gnomad4 ASJ exome AF: 0.410

Gnomad4 EAS exome AF: 0.225

Gnomad4 SAS exome AF: 0.465

Gnomad4 FIN exome AF: 0.404

Gnomad4 NFE exome AF: 0.460

Gnomad4 OTH exome AF: 0.441

GnomAD4 genome AF: 0.443 AC: 67431 AN: 152088 Hom.: 15184 Cov.: 33 AF XY: 0.441 AC XY: 32773 AN XY: 74366

Gnomad4 AFR AF: 0.460

Gnomad4 AMR AF: 0.433

Gnomad4 ASJ AF: 0.409

Gnomad4 EAS AF: 0.232

Gnomad4 SAS AF: 0.454

Gnomad4 FIN AF: 0.396

Gnomad4 NFE AF: 0.458

Gnomad4 OTH AF: 0.452

Alfa AF: 0.459 Hom.: 25555

Bravo AF: 0.447

Asia WGS AF: 0.370 AC: 1288 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.66
DANN	Benign	0.33

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: rs3740057; hg19: chr10-101658585; COSMIC: COSV60625762;