rs3740058

Variant names:

• chr10-99896225-G-A
• rs3740058
• NM_015221.4:c.3051+42C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 8 publications found

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 Gene-Disease associations (from GenCC):

• cataract 48

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• total early-onset cataract

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015221.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNMBP	NM_015221.4	MANE Select	c.3051+42C>T		intron	N/A	NP_056036.1	Q6XZF7-1
	DNMBP	NM_001441287.1		c.3051+42C>T		intron	N/A	NP_001428216.1
	DNMBP	NM_001441288.1		c.3051+42C>T		intron	N/A	NP_001428217.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNMBP	ENST00000324109.9	TSL:1 MANE Select	c.3051+42C>T		intron	N/A	ENSP00000315659.4	Q6XZF7-1
	DNMBP	ENST00000543621.6	TSL:1	c.915+42C>T		intron	N/A	ENSP00000443657.2	A0A1C7CYY6
	DNMBP	ENST00000856964.1		c.3051+42C>T		intron	N/A	ENSP00000527023.1

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

GnomAD2 exomes AF: 0.343 AC: 83245 AN: 242434 AF XY: 0.349

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 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

African (AFR) AF: 0.191 AC: 6333 AN: 33224

American (AMR) AF: 0.342 AC: 15032 AN: 43932

Ashkenazi Jewish (ASJ) AF: 0.347 AC: 8926 AN: 25724

East Asian (EAS) AF: 0.203 AC: 7984 AN: 39422

South Asian (SAS) AF: 0.354 AC: 30134 AN: 85088

European-Finnish (FIN) AF: 0.347 AC: 18385 AN: 53012

Middle Eastern (MID) AF: 0.289 AC: 1652 AN: 5714

European-Non Finnish (NFE) AF: 0.393 AC: 433148 AN: 1102758

Other (OTH) AF: 0.360 AC: 21512 AN: 59828

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

African (AFR) AF: 0.198 AC: 8214 AN: 41486

American (AMR) AF: 0.335 AC: 5114 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.344 AC: 1195 AN: 3470

East Asian (EAS) AF: 0.209 AC: 1082 AN: 5174

South Asian (SAS) AF: 0.344 AC: 1659 AN: 4826

European-Finnish (FIN) AF: 0.337 AC: 3560 AN: 10550

Middle Eastern (MID) AF: 0.305 AC: 89 AN: 292

European-Non Finnish (NFE) AF: 0.382 AC: 25991 AN: 67962

Other (OTH) AF: 0.331 AC: 700 AN: 2112

Alfa AF: 0.351 Hom.: 4268

Bravo AF: 0.310

Asia WGS AF: 0.270 AC: 938 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	5.2
DANN	Benign	0.86
PhyloP100		0.11
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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