10-99930364-C-T

Variant names:

• chr10-99930364-C-T
• rs115073424
• NM_015221.4:c.2261-21218G>A

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6 BS1 BS2

The NM_001318326.2(DNMBP):​c.400G>A​(p.Gly134Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0021 in 702,966 control chromosomes in the GnomAD database, including 14 homozygotes. In-silico tool predicts a benign outcome for this variant. 8/9 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.0067 (12 hom., cov: 32)
  • Exomes 𝑓: 0.00081 (2 hom.)
• Consequence: DNMBP NM_001318326.2 missense
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: -1.67
• Publications: 0 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 (MetaRNN=0.0032663643).
• BP6: Variant 10-99930364-C-T is Benign according to our data. Variant chr10-99930364-C-T is described in ClinVar as Benign. ClinVar VariationId is 3042017.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00674 (1026/152268) while in subpopulation AFR AF = 0.0235 (977/41536). AF 95% confidence interval is 0.0223. There are 12 homozygotes in GnomAd4. There are 493 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 12 AD,AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001318326.2. 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.2261-21218G>A		intron	N/A	NP_056036.1	Q6XZF7-1
	DNMBP	NM_001318326.2		c.400G>A	p.Gly134Arg	missense	Exon 1 of 14	NP_001305255.1	A0A1B0GTX1
	DNMBP	NM_001441287.1		c.2261-21218G>A		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.2261-21218G>A		intron	N/A	ENSP00000315659.4	Q6XZF7-1
	DNMBP	ENST00000636706.1	TSL:2	c.400G>A	p.Gly134Arg	missense	Exon 1 of 14	ENSP00000489875.1	A0A1B0GTX1
	DNMBP	ENST00000856964.1		c.2261-21218G>A		intron	N/A	ENSP00000527023.1

Frequencies

GnomAD3 genomes AF: 0.00673 AC: 1024 AN: 152150 Hom.: 12 Cov.: 32

Gnomad AFR AF: 0.0235

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00203

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.0000942

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000103

Gnomad OTH AF: 0.00478

GnomAD2 exomes AF: 0.00132 AC: 178 AN: 134496 AF XY: 0.00115

Gnomad AFR exome AF: 0.0244

Gnomad AMR exome AF: 0.000736

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000379

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000812 AC: 447 AN: 550698 Hom.: 2 Cov.: 0 AF XY: 0.000641 AC XY: 191 AN XY: 298128

African (AFR) AF: 0.0223 AC: 352 AN: 15808

American (AMR) AF: 0.00101 AC: 35 AN: 34712

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20030

East Asian (EAS) AF: 0.00 AC: 0 AN: 32104

South Asian (SAS) AF: 0.0000478 AC: 3 AN: 62770

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33618

Middle Eastern (MID) AF: 0.000491 AC: 2 AN: 4076

European-Non Finnish (NFE) AF: 0.0000221 AC: 7 AN: 316974

Other (OTH) AF: 0.00157 AC: 48 AN: 30606

GnomAD4 genome AF: 0.00674 AC: 1026 AN: 152268 Hom.: 12 Cov.: 32 AF XY: 0.00662 AC XY: 493 AN XY: 74464

African (AFR) AF: 0.0235 AC: 977 AN: 41536

American (AMR) AF: 0.00203 AC: 31 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.0000942 AC: 1 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000103 AC: 7 AN: 68024

Other (OTH) AF: 0.00473 AC: 10 AN: 2112

Alfa AF: 0.00794 Hom.: 1

Bravo AF: 0.00727

ExAC AF: 0.00119 AC: 20

Asia WGS AF: 0.000577 AC: 2 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
AlphaMissense	Benign	0.078
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.28
DANN	Benign	0.55
FATHMM_MKL	Benign	0.024	N
LIST_S2	Benign	0.36	T
MetaRNN	Benign	0.0033	T
PhyloP100		-1.7
GERP RS		-3.5
Mutation Taster		=299/1	polymorphism

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: rs115073424; hg19: chr10-101690121;