rs10883421

chr10-99912584-A-G

Variant summary

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

The NM_015221.4(DNMBP):c.2261-3438T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.442 in 152,008 control chromosomes in the GnomAD database, including 15,081 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 (15081 hom., cov: 32)
• Consequence: DNMBP NM_015221.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.599

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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.454 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNMBP	NM_015221.4	c.2261-3438T>C		intron_variant		ENST00000324109.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNMBP	ENST00000324109.9	c.2261-3438T>C		intron_variant		1	NM_015221.4	P1
DNMBP	ENST00000543621.6	c.124+1369T>C		intron_variant		1
DNMBP	ENST00000636706.1	c.1157-3438T>C		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.442 AC: 67134 AN: 151890 Hom.: 15074 Cov.: 32

Gnomad AFR AF: 0.456

Gnomad AMI AF: 0.542

Gnomad AMR AF: 0.433

Gnomad ASJ AF: 0.409

Gnomad EAS AF: 0.232

Gnomad SAS AF: 0.455

Gnomad FIN AF: 0.396

Gnomad MID AF: 0.383

Gnomad NFE AF: 0.458

Gnomad OTH AF: 0.448

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.442 AC: 67186 AN: 152008 Hom.: 15081 Cov.: 32 AF XY: 0.439 AC XY: 32609 AN XY: 74268

Gnomad4 AFR AF: 0.455

Gnomad4 AMR AF: 0.433

Gnomad4 ASJ AF: 0.409

Gnomad4 EAS AF: 0.231

Gnomad4 SAS AF: 0.454

Gnomad4 FIN AF: 0.396

Gnomad4 NFE AF: 0.458

Gnomad4 OTH AF: 0.451

Alfa AF: 0.450 Hom.: 5010

Bravo AF: 0.445

Asia WGS AF: 0.370 AC: 1287 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	5.8
Dann	Benign	0.59

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: rs10883421; hg19: chr10-101672341;