rs4078288

Positions:

• chr18-53020881-G-A
• chr18-53020881-G-C

Variant summary

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

The NM_005215.4(DCC):​c.986-42424G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.727 in 151,830 control chromosomes in the GnomAD database, including 40,313 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 0.73 (40313 hom., cov: 30)
• Consequence: DCC NM_005215.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.384

Genes affected

DCC (HGNC:2701): (DCC netrin 1 receptor) This gene encodes a netrin 1 receptor. The transmembrane protein is a member of the immunoglobulin superfamily of cell adhesion molecules, and mediates axon guidance of neuronal growth cones towards sources of netrin 1 ligand. The cytoplasmic tail interacts with the tyrosine kinases Src and focal adhesion kinase (FAK, also known as PTK2) to mediate axon attraction. The protein partially localizes to lipid rafts, and induces apoptosis in the absence of ligand. The protein functions as a tumor suppressor, and is frequently mutated or downregulated in colorectal cancer and esophageal carcinoma. [provided by RefSeq, Oct 2009]

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 (EAS) allele frequency at 95% confidence interval = 0.734 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DCC	NM_005215.4	c.986-42424G>A		intron_variant		ENST00000442544.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DCC	ENST00000442544.7	c.986-42424G>A		intron_variant		1	NM_005215.4	P1

Frequencies

GnomAD3 genomes AF: 0.727 AC: 110318 AN: 151712 Hom.: 40281 Cov.: 30

Gnomad AFR AF: 0.735

Gnomad AMI AF: 0.594

Gnomad AMR AF: 0.674

Gnomad ASJ AF: 0.754

Gnomad EAS AF: 0.750

Gnomad SAS AF: 0.717

Gnomad FIN AF: 0.688

Gnomad MID AF: 0.726

Gnomad NFE AF: 0.740

Gnomad OTH AF: 0.728

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

GnomAD4 genome AF: 0.727 AC: 110405 AN: 151830 Hom.: 40313 Cov.: 30 AF XY: 0.726 AC XY: 53869 AN XY: 74200

Gnomad4 AFR AF: 0.735

Gnomad4 AMR AF: 0.674

Gnomad4 ASJ AF: 0.754

Gnomad4 EAS AF: 0.750

Gnomad4 SAS AF: 0.716

Gnomad4 FIN AF: 0.688

Gnomad4 NFE AF: 0.740

Gnomad4 OTH AF: 0.727

Alfa AF: 0.735 Hom.: 18719

Bravo AF: 0.722

Asia WGS AF: 0.747 AC: 2598 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	0.13
DANN	Benign	0.37

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: rs4078288; hg19: chr18-50547251;