NM_015221.4:c.2261-21476T>C

Variant names:

• chr10-99930622-A-G
• rs10883428
• NM_015221.4:c.2261-21476T>C

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_015221.4(DNMBP):​c.2261-21476T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.378 in 702,500 control chromosomes in the GnomAD database, including 51,166 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.40 (12257 hom., cov: 31)
  • Exomes 𝑓: 0.37 (38909 hom.)
• Consequence: DNMBP NM_015221.4 intron
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 1.38
• 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-AS1 (HGNC:20431): (DNMBP antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 10-99930622-A-G is Benign according to our data. Variant chr10-99930622-A-G is described in ClinVar as Benign. ClinVar VariationId is 3059290.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.467 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.2261-21476T>C		intron	N/A	NP_056036.1	Q6XZF7-1
	DNMBP	NM_001318326.2		c.142T>C	p.Leu48Leu	synonymous	Exon 1 of 14	NP_001305255.1	A0A1B0GTX1
	DNMBP	NM_001441287.1		c.2261-21476T>C		intron	N/A	NP_001428216.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNMBP	ENST00000324109.9	TSL:1 MANE Select	c.2261-21476T>C		intron	N/A	ENSP00000315659.4	Q6XZF7-1
	DNMBP	ENST00000636706.1	TSL:2	c.142T>C	p.Leu48Leu	synonymous	Exon 1 of 14	ENSP00000489875.1	A0A1B0GTX1
	DNMBP	ENST00000856964.1		c.2261-21476T>C		intron	N/A	ENSP00000527023.1

Frequencies

GnomAD3 genomes AF: 0.399 AC: 60550 AN: 151756 Hom.: 12248 Cov.: 31

Gnomad AFR AF: 0.472

Gnomad AMI AF: 0.506

Gnomad AMR AF: 0.394

Gnomad ASJ AF: 0.358

Gnomad EAS AF: 0.251

Gnomad SAS AF: 0.344

Gnomad FIN AF: 0.324

Gnomad MID AF: 0.399

Gnomad NFE AF: 0.383

Gnomad OTH AF: 0.397

GnomAD2 exomes AF: 0.373 AC: 50228 AN: 134488 AF XY: 0.369

Gnomad AFR exome AF: 0.478

Gnomad AMR exome AF: 0.419

Gnomad ASJ exome AF: 0.352

Gnomad EAS exome AF: 0.252

Gnomad FIN exome AF: 0.333

Gnomad NFE exome AF: 0.384

Gnomad OTH exome AF: 0.397

GnomAD4 exome AF: 0.373 AC: 205276 AN: 550626 Hom.: 38909 Cov.: 0 AF XY: 0.370 AC XY: 110418 AN XY: 298084

African (AFR) AF: 0.479 AC: 7573 AN: 15806

American (AMR) AF: 0.414 AC: 14354 AN: 34694

Ashkenazi Jewish (ASJ) AF: 0.355 AC: 7100 AN: 20026

East Asian (EAS) AF: 0.249 AC: 7985 AN: 32104

South Asian (SAS) AF: 0.342 AC: 21480 AN: 62762

European-Finnish (FIN) AF: 0.335 AC: 11246 AN: 33608

Middle Eastern (MID) AF: 0.366 AC: 1491 AN: 4076

European-Non Finnish (NFE) AF: 0.386 AC: 122364 AN: 316948

Other (OTH) AF: 0.382 AC: 11683 AN: 30602

GnomAD4 genome AF: 0.399 AC: 60605 AN: 151874 Hom.: 12257 Cov.: 31 AF XY: 0.396 AC XY: 29377 AN XY: 74246

African (AFR) AF: 0.472 AC: 19549 AN: 41400

American (AMR) AF: 0.394 AC: 6012 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.358 AC: 1242 AN: 3466

East Asian (EAS) AF: 0.250 AC: 1290 AN: 5150

South Asian (SAS) AF: 0.343 AC: 1652 AN: 4810

European-Finnish (FIN) AF: 0.324 AC: 3413 AN: 10548

Middle Eastern (MID) AF: 0.384 AC: 113 AN: 294

European-Non Finnish (NFE) AF: 0.383 AC: 26035 AN: 67922

Other (OTH) AF: 0.398 AC: 840 AN: 2108

Alfa AF: 0.392 Hom.: 21085

Bravo AF: 0.408

Asia WGS AF: 0.301 AC: 1043 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	DNMBP-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	13
DANN	Benign	0.63
PhyloP100		1.4
PromoterAI		0.015	Neutral
Mutation Taster		=299/1	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: rs10883428; hg19: chr10-101690379; COSMIC: COSV60625436; COSMIC: COSV60625436;