rs2070515

chr21-36231355-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001320714.2(DOP1B):c.2350+221A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.359 in 152,148 control chromosomes in the GnomAD database, including 11,545 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 0.36 (11545 hom., cov: 33)
• Consequence: DOP1B NM_001320714.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.05

Genes affected

DOP1B (HGNC:1291): (DOP1 leucine zipper like protein B) Involved in cognition. Located in early endosome membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.478 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DOP1B	NM_001320714.2	c.2350+221A>G		intron_variant		ENST00000691173.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DOP1B	ENST00000691173.1	c.2350+221A>G		intron_variant			NM_001320714.2	P1
DOP1B	ENST00000399151.3	c.2350+221A>G		intron_variant		1		P1
DOP1B	ENST00000685394.1	c.2350+221A>G		intron_variant, NMD_transcript_variant
DOP1B	ENST00000693273.1	c.*1325+221A>G		intron_variant, NMD_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.359 AC: 54630 AN: 152030 Hom.: 11547 Cov.: 33

Gnomad AFR AF: 0.130

Gnomad AMI AF: 0.589

Gnomad AMR AF: 0.393

Gnomad ASJ AF: 0.491

Gnomad EAS AF: 0.417

Gnomad SAS AF: 0.495

Gnomad FIN AF: 0.329

Gnomad MID AF: 0.427

Gnomad NFE AF: 0.472

Gnomad OTH AF: 0.368

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

GnomAD4 genome AF: 0.359 AC: 54614 AN: 152148 Hom.: 11545 Cov.: 33 AF XY: 0.357 AC XY: 26527 AN XY: 74350

Gnomad4 AFR AF: 0.130

Gnomad4 AMR AF: 0.392

Gnomad4 ASJ AF: 0.491

Gnomad4 EAS AF: 0.417

Gnomad4 SAS AF: 0.494

Gnomad4 FIN AF: 0.329

Gnomad4 NFE AF: 0.472

Gnomad4 OTH AF: 0.364

Alfa AF: 0.453 Hom.: 22228

Bravo AF: 0.354

Asia WGS AF: 0.444 AC: 1547 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	5.2
Dann	Benign	0.63

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2070515; hg19: chr21-37603653;