rs61927768

Positions:

• chr12-50504945-G-A
• chr12-50504945-G-T

Variant summary

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

The 12-50504945-G-A variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.272 in 533,844 control chromosomes in the GnomAD database, including 31,510 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 0.20 (3824 hom., cov: 32)
  • Exomes 𝑓: 0.30 (27686 hom.)
• Consequence: DIP2B NM_173602.3 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.69

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=-0.48).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.293 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DIP2B	NM_173602.3			upstream_gene_variant		ENST00000301180.10	NP_775873.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DIP2B	ENST00000301180.10			upstream_gene_variant		5	NM_173602.3	ENSP00000301180	P1
DIP2B	ENST00000549620.5			upstream_gene_variant		1

Frequencies

GnomAD3 genomes AF: 0.199 AC: 29843 AN: 149824 Hom.: 3824 Cov.: 32

Gnomad AFR AF: 0.0562

Gnomad AMI AF: 0.186

Gnomad AMR AF: 0.167

Gnomad ASJ AF: 0.175

Gnomad EAS AF: 0.0611

Gnomad SAS AF: 0.241

Gnomad FIN AF: 0.240

Gnomad MID AF: 0.211

Gnomad NFE AF: 0.296

Gnomad OTH AF: 0.226

GnomAD4 exome AF: 0.301 AC: 115416 AN: 383896 Hom.: 27686 Cov.: 4 AF XY: 0.300 AC XY: 62368 AN XY: 207948

Gnomad4 AFR exome AF: 0.0608

Gnomad4 AMR exome AF: 0.174

Gnomad4 ASJ exome AF: 0.236

Gnomad4 EAS exome AF: 0.0692

Gnomad4 SAS exome AF: 0.279

Gnomad4 FIN exome AF: 0.295

Gnomad4 NFE exome AF: 0.352

Gnomad4 OTH exome AF: 0.292

GnomAD4 genome AF: 0.199 AC: 29837 AN: 149948 Hom.: 3824 Cov.: 32 AF XY: 0.195 AC XY: 14292 AN XY: 73224

Gnomad4 AFR AF: 0.0560

Gnomad4 AMR AF: 0.166

Gnomad4 ASJ AF: 0.175

Gnomad4 EAS AF: 0.0610

Gnomad4 SAS AF: 0.242

Gnomad4 FIN AF: 0.240

Gnomad4 NFE AF: 0.296

Gnomad4 OTH AF: 0.224

Alfa AF: 0.127 Hom.: 247

Bravo AF: 0.184

Asia WGS AF: 0.155 AC: 538 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
CADD	Benign	17
DANN	Benign	0.97

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs61927768; hg19: chr12-50898728; COSMIC: COSV56594422;