NM_015018.4:c.-146-14189A>G

Variant names:

• chr6-83082542-A-G
• rs2182233
• NM_015018.4:c.-146-14189A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015018.4(DOP1A):​c.-146-14189A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.787 in 152,094 control chromosomes in the GnomAD database, including 47,187 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 0.79 (47187 hom., cov: 32)
• Consequence: DOP1A NM_015018.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.792
• Publications: 5 publications found

Genes affected

DOP1A (HGNC:21194): (DOP1 leucine zipper like protein A) Predicted to be involved in Golgi to endosome transport and endoplasmic reticulum organization. Predicted to be located in Golgi membrane. Predicted to be active in endosome and trans-Golgi network. [provided by Alliance of Genome Resources, Apr 2022]

DOP1A Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.04).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.817 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DOP1A	NM_015018.4	c.-146-14189A>G		intron_variant	Intron 1 of 38	ENST00000349129.7	NP_055833.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DOP1A	ENST00000349129.7	c.-146-14189A>G		intron_variant	Intron 1 of 38	1	NM_015018.4	ENSP00000195654.3
DOP1A	ENST00000237163.9	c.-146-14189A>G		intron_variant	Intron 1 of 39	5		ENSP00000237163.6

Frequencies

GnomAD3 genomes AF: 0.787 AC: 119566 AN: 151976 Hom.: 47144 Cov.: 32

Gnomad AFR AF: 0.816

Gnomad AMI AF: 0.852

Gnomad AMR AF: 0.813

Gnomad ASJ AF: 0.812

Gnomad EAS AF: 0.801

Gnomad SAS AF: 0.839

Gnomad FIN AF: 0.748

Gnomad MID AF: 0.832

Gnomad NFE AF: 0.762

Gnomad OTH AF: 0.793

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.787 AC: 119669 AN: 152094 Hom.: 47187 Cov.: 32 AF XY: 0.788 AC XY: 58578 AN XY: 74338

African (AFR) AF: 0.816 AC: 33872 AN: 41502

American (AMR) AF: 0.813 AC: 12430 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.812 AC: 2815 AN: 3468

East Asian (EAS) AF: 0.802 AC: 4136 AN: 5160

South Asian (SAS) AF: 0.839 AC: 4046 AN: 4822

European-Finnish (FIN) AF: 0.748 AC: 7906 AN: 10574

Middle Eastern (MID) AF: 0.833 AC: 245 AN: 294

European-Non Finnish (NFE) AF: 0.762 AC: 51770 AN: 67970

Other (OTH) AF: 0.794 AC: 1672 AN: 2106

Alfa AF: 0.771 Hom.: 8453

Bravo AF: 0.791

Asia WGS AF: 0.836 AC: 2907 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.33
DANN	Benign	0.49
PhyloP100		-0.79
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: rs2182233; hg19: chr6-83792261;