rs6584331

Variant names:

• chr10-99909229-T-C
• rs6584331
• NM_015221.4:c.2261-83A>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.2261-83A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.503 in 1,084,692 control chromosomes in the GnomAD database, including 140,985 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 0.52 (20944 hom., cov: 32)
  • Exomes 𝑓: 0.50 (120041 hom.)
• Consequence: DNMBP NM_015221.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0750
• Publications: 3 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.59 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNMBP	NM_015221.4	c.2261-83A>G		intron_variant	Intron 4 of 16	ENST00000324109.9	NP_056036.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNMBP	ENST00000324109.9	c.2261-83A>G		intron_variant	Intron 4 of 16	1	NM_015221.4	ENSP00000315659.4
DNMBP	ENST00000543621.6	c.125-83A>G		intron_variant	Intron 1 of 13	1		ENSP00000443657.2
DNMBP	ENST00000636706.1	c.1157-83A>G		intron_variant	Intron 1 of 13	2		ENSP00000489875.1

Frequencies

GnomAD3 genomes AF: 0.518 AC: 78618 AN: 151836 Hom.: 20914 Cov.: 32

Gnomad AFR AF: 0.596

Gnomad AMI AF: 0.568

Gnomad AMR AF: 0.505

Gnomad ASJ AF: 0.487

Gnomad EAS AF: 0.232

Gnomad SAS AF: 0.483

Gnomad FIN AF: 0.418

Gnomad MID AF: 0.611

Gnomad NFE AF: 0.513

Gnomad OTH AF: 0.540

GnomAD4 exome AF: 0.501 AC: 467403 AN: 932738 Hom.: 120041 AF XY: 0.502 AC XY: 236872 AN XY: 472142

African (AFR) AF: 0.599 AC: 13176 AN: 22000

American (AMR) AF: 0.484 AC: 11461 AN: 23662

Ashkenazi Jewish (ASJ) AF: 0.498 AC: 8763 AN: 17590

East Asian (EAS) AF: 0.226 AC: 8072 AN: 35754

South Asian (SAS) AF: 0.491 AC: 29095 AN: 59304

European-Finnish (FIN) AF: 0.430 AC: 15828 AN: 36838

Middle Eastern (MID) AF: 0.537 AC: 1682 AN: 3130

European-Non Finnish (NFE) AF: 0.518 AC: 358267 AN: 692296

Other (OTH) AF: 0.499 AC: 21059 AN: 42164

GnomAD4 genome AF: 0.518 AC: 78708 AN: 151954 Hom.: 20944 Cov.: 32 AF XY: 0.512 AC XY: 38047 AN XY: 74254

African (AFR) AF: 0.596 AC: 24699 AN: 41436

American (AMR) AF: 0.504 AC: 7687 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.487 AC: 1689 AN: 3468

East Asian (EAS) AF: 0.232 AC: 1198 AN: 5174

South Asian (SAS) AF: 0.483 AC: 2327 AN: 4818

European-Finnish (FIN) AF: 0.418 AC: 4405 AN: 10546

Middle Eastern (MID) AF: 0.616 AC: 181 AN: 294

European-Non Finnish (NFE) AF: 0.513 AC: 34859 AN: 67956

Other (OTH) AF: 0.544 AC: 1148 AN: 2112

Alfa AF: 0.525 Hom.: 26985

Bravo AF: 0.528

Asia WGS AF: 0.401 AC: 1394 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	9.6
DANN	Benign	0.55
PhyloP100		-0.075
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs6584331; hg19: chr10-101668986; COSMIC: COSV60623672;