rs4973194

Positions:

• chr2-229372761-G-A
• chr2-229372761-G-C

Variant summary

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

The NM_139072.4(DNER):​c.1856-5642C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.693 in 151,882 control chromosomes in the GnomAD database, including 36,853 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 0.69 (36853 hom., cov: 30)
• Consequence: DNER NM_139072.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.247

Genes affected

DNER (HGNC:24456): (delta/notch like EGF repeat containing) Predicted to enable Notch binding activity. Involved in central nervous system development. Located in dendrite; early endosome; and plasma 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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.885 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNER	NM_139072.4	c.1856-5642C>T		intron_variant		ENST00000341772.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNER	ENST00000341772.5	c.1856-5642C>T		intron_variant		1	NM_139072.4	P1

Frequencies

GnomAD3 genomes AF: 0.693 AC: 105103 AN: 151764 Hom.: 36809 Cov.: 30

Gnomad AFR AF: 0.740

Gnomad AMI AF: 0.626

Gnomad AMR AF: 0.744

Gnomad ASJ AF: 0.656

Gnomad EAS AF: 0.906

Gnomad SAS AF: 0.648

Gnomad FIN AF: 0.671

Gnomad MID AF: 0.661

Gnomad NFE AF: 0.646

Gnomad OTH AF: 0.688

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

GnomAD4 genome AF: 0.693 AC: 105203 AN: 151882 Hom.: 36853 Cov.: 30 AF XY: 0.696 AC XY: 51632 AN XY: 74210

Gnomad4 AFR AF: 0.740

Gnomad4 AMR AF: 0.744

Gnomad4 ASJ AF: 0.656

Gnomad4 EAS AF: 0.906

Gnomad4 SAS AF: 0.647

Gnomad4 FIN AF: 0.671

Gnomad4 NFE AF: 0.646

Gnomad4 OTH AF: 0.691

Alfa AF: 0.652 Hom.: 43187

Bravo AF: 0.703

Asia WGS AF: 0.784 AC: 2723 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.1
DANN	Benign	0.38

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: rs4973194; hg19: chr2-230237477;