NM_015221.4:c.2703-68A>G

Variant names:

• chr10-99898828-T-C
• rs3740057
• NM_015221.4:c.2703-68A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 10 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=-0.94).
• 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 rank	MANE	Protein	UniProt
DNMBP	NM_015221.4	c.2703-68A>G		intron_variant	Intron 7 of 16	ENST00000324109.9	NP_056036.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNMBP	ENST00000324109.9	c.2703-68A>G		intron_variant	Intron 7 of 16	1	NM_015221.4	ENSP00000315659.4
DNMBP	ENST00000543621.6	c.567-68A>G		intron_variant	Intron 4 of 13	1		ENSP00000443657.2
DNMBP	ENST00000636706.1	c.1599-68A>G		intron_variant	Intron 4 of 13	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

African (AFR) AF: 0.464 AC: 13140 AN: 28290

American (AMR) AF: 0.431 AC: 17166 AN: 39856

Ashkenazi Jewish (ASJ) AF: 0.410 AC: 9969 AN: 24302

East Asian (EAS) AF: 0.225 AC: 8699 AN: 38662

South Asian (SAS) AF: 0.465 AC: 36771 AN: 79024

European-Finnish (FIN) AF: 0.404 AC: 21115 AN: 52300

Middle Eastern (MID) AF: 0.382 AC: 2021 AN: 5290

European-Non Finnish (NFE) AF: 0.460 AC: 426677 AN: 926930

Other (OTH) AF: 0.441 AC: 23422 AN: 53132

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

African (AFR) AF: 0.460 AC: 19096 AN: 41486

American (AMR) AF: 0.433 AC: 6626 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.409 AC: 1418 AN: 3468

East Asian (EAS) AF: 0.232 AC: 1198 AN: 5160

South Asian (SAS) AF: 0.454 AC: 2191 AN: 4822

European-Finnish (FIN) AF: 0.396 AC: 4193 AN: 10588

Middle Eastern (MID) AF: 0.387 AC: 113 AN: 292

European-Non Finnish (NFE) AF: 0.458 AC: 31151 AN: 67966

Other (OTH) AF: 0.452 AC: 953 AN: 2110

Alfa AF: 0.455 Hom.: 57706

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
PhyloP100		-1.7
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: rs3740057; hg19: chr10-101658585; COSMIC: COSV60625762;