rs10876043

Positions:

• chr12-50510361-A-G

Variant summary

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

The NM_173602.3(DIP2B):​c.100+5121A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.246 in 152,156 control chromosomes in the GnomAD database, including 5,374 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 0.25 (5374 hom., cov: 32)
• Consequence: DIP2B NM_173602.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.23

Genes affected

DIP2B (HGNC:29284): (disco interacting protein 2 homolog B) This gene encodes a member of the disco-interacting protein homolog 2 protein family. The encoded protein contains a binding site for the transcriptional regulator DNA methyltransferase 1 associated protein 1 as well as AMP-binding sites. The presence of these sites suggests that the encoded protein may participate in DNA methylation. This gene is located near a folate-sensitive fragile site, and CGG-repeat expansion in the promoter of this gene which affects transcription has been detected in individuals containing this fragile site on chromosome 12. [provided by RefSeq, Aug 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.356 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DIP2B	NM_173602.3	c.100+5121A>G		intron_variant		ENST00000301180.10	NP_775873.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DIP2B	ENST00000301180.10	c.100+5121A>G		intron_variant		5	NM_173602.3	ENSP00000301180	P1
DIP2B	ENST00000549620.5	n.256+5121A>G		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.246 AC: 37462 AN: 152038 Hom.: 5359 Cov.: 32

Gnomad AFR AF: 0.0984

Gnomad AMI AF: 0.367

Gnomad AMR AF: 0.310

Gnomad ASJ AF: 0.284

Gnomad EAS AF: 0.369

Gnomad SAS AF: 0.322

Gnomad FIN AF: 0.364

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.286

Gnomad OTH AF: 0.238

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

GnomAD4 genome AF: 0.246 AC: 37499 AN: 152156 Hom.: 5374 Cov.: 32 AF XY: 0.255 AC XY: 18973 AN XY: 74388

Gnomad4 AFR AF: 0.0985

Gnomad4 AMR AF: 0.311

Gnomad4 ASJ AF: 0.284

Gnomad4 EAS AF: 0.369

Gnomad4 SAS AF: 0.322

Gnomad4 FIN AF: 0.364

Gnomad4 NFE AF: 0.286

Gnomad4 OTH AF: 0.244

Alfa AF: 0.330 Hom.: 2483

Bravo AF: 0.234

Asia WGS AF: 0.330 AC: 1144 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.73
DANN	Benign	0.73

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: rs10876043; hg19: chr12-50904144;