rs1054442

chr12-48995537-A-Cchr12-48995537-A-Gchr12-48995537-A-T

Variant summary

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

The NM_015086.2(DDN):c.*1203T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.452 in 152,290 control chromosomes in the GnomAD database, including 16,555 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 0.45 (16540 hom., cov: 33)
  • Exomes 𝑓: 0.43 (15 hom.)
• Consequence: DDN NM_015086.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.118

Genes affected

DDN (HGNC:24458): (dendrin) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to act upstream of or within positive regulation of transcription by RNA polymerase II. Located in cell projection and cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.616 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DDN	NM_015086.2	c.*1203T>G		3_prime_UTR_variant	2/2	ENST00000421952.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DDN	ENST00000421952.3	c.*1203T>G		3_prime_UTR_variant	2/2	1	NM_015086.2	P1
	ENST00000549516.1	n.205+183A>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.452 AC: 68689 AN: 152022 Hom.: 16504 Cov.: 33

Gnomad AFR AF: 0.622

Gnomad AMI AF: 0.486

Gnomad AMR AF: 0.355

Gnomad ASJ AF: 0.302

Gnomad EAS AF: 0.424

Gnomad SAS AF: 0.506

Gnomad FIN AF: 0.433

Gnomad MID AF: 0.320

Gnomad NFE AF: 0.381

Gnomad OTH AF: 0.389

GnomAD4 exome AF: 0.433 AC: 65 AN: 150 Hom.: 15 Cov.: 0 AF XY: 0.445 AC XY: 49 AN XY: 110

Gnomad4 AMR exome AF: 1.00

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 0.500

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.405

Gnomad4 OTH exome AF: 0.417

GnomAD4 genome AF: 0.452 AC: 68780 AN: 152140 Hom.: 16540 Cov.: 33 AF XY: 0.452 AC XY: 33596 AN XY: 74376

Gnomad4 AFR AF: 0.622

Gnomad4 AMR AF: 0.354

Gnomad4 ASJ AF: 0.302

Gnomad4 EAS AF: 0.424

Gnomad4 SAS AF: 0.506

Gnomad4 FIN AF: 0.433

Gnomad4 NFE AF: 0.381

Gnomad4 OTH AF: 0.388

Alfa AF: 0.376 Hom.: 12424

Bravo AF: 0.444

Asia WGS AF: 0.461 AC: 1603 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
Cadd	Benign	9.2
Dann	Benign	0.35

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: rs1054442; hg19: chr12-49389320;