rs7280062

chr21-36234372-T-C

Variant summary

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

The NM_001320714.2(DOP1B):c.2622+1297T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.289 in 151,952 control chromosomes in the GnomAD database, including 6,961 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 0.29 (6961 hom., cov: 31)
• Consequence: DOP1B NM_001320714.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.187

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=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.531 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DOP1B	NM_001320714.2	c.2622+1297T>C		intron_variant		ENST00000691173.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DOP1B	ENST00000691173.1	c.2622+1297T>C		intron_variant			NM_001320714.2	P1
DOP1B	ENST00000399151.3	c.2622+1297T>C		intron_variant		1		P1
DOP1B	ENST00000685394.1	c.2622+1297T>C		intron_variant, NMD_transcript_variant
DOP1B	ENST00000693273.1	c.*1597+1297T>C		intron_variant, NMD_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.288 AC: 43782 AN: 151834 Hom.: 6944 Cov.: 31

Gnomad AFR AF: 0.365

Gnomad AMI AF: 0.207

Gnomad AMR AF: 0.238

Gnomad ASJ AF: 0.198

Gnomad EAS AF: 0.547

Gnomad SAS AF: 0.390

Gnomad FIN AF: 0.405

Gnomad MID AF: 0.223

Gnomad NFE AF: 0.215

Gnomad OTH AF: 0.253

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

GnomAD4 genome AF: 0.289 AC: 43849 AN: 151952 Hom.: 6961 Cov.: 31 AF XY: 0.300 AC XY: 22278 AN XY: 74274

Gnomad4 AFR AF: 0.365

Gnomad4 AMR AF: 0.238

Gnomad4 ASJ AF: 0.198

Gnomad4 EAS AF: 0.547

Gnomad4 SAS AF: 0.390

Gnomad4 FIN AF: 0.405

Gnomad4 NFE AF: 0.215

Gnomad4 OTH AF: 0.260

Alfa AF: 0.228 Hom.: 8611

Bravo AF: 0.279

Asia WGS AF: 0.435 AC: 1509 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
Cadd	Benign	1.1
Dann	Benign	0.80

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

Publications

LitVar

Other links and lift over

dbSNP: rs7280062; hg19: chr21-37606670;