rs4618569

Positions:

• chr6-30887474-G-A
• chr6-30887474-G-T

Variant summary

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

The NM_001297654.2(DDR1):​c.-42-1214G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.262 in 151,858 control chromosomes in the GnomAD database, including 6,162 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 0.26 (6162 hom., cov: 32)
• Consequence: DDR1 NM_001297654.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.364

Genes affected

DDR1 (HGNC:2730): (discoidin domain receptor tyrosine kinase 1) Receptor tyrosine kinases play a key role in the communication of cells with their microenvironment. These kinases are involved in the regulation of cell growth, differentiation and metabolism. The protein encoded by this gene belongs to a subfamily of tyrosine kinase receptors with homology to Dictyostelium discoideum protein discoidin I in their extracellular domain, and that are activated by various types of collagen. Expression of this protein is restricted to epithelial cells, particularly in the kidney, lung, gastrointestinal tract, and brain. In addition, it has been shown to be significantly overexpressed in several human tumors. Alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Feb 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.595 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DDR1	NM_001297654.2	c.-42-1214G>A		intron_variant		ENST00000376568.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DDR1	ENST00000376568.8	c.-42-1214G>A		intron_variant		1	NM_001297654.2	P1

Frequencies

GnomAD3 genomes AF: 0.262 AC: 39729 AN: 151740 Hom.: 6146 Cov.: 32

Gnomad AFR AF: 0.273

Gnomad AMI AF: 0.301

Gnomad AMR AF: 0.365

Gnomad ASJ AF: 0.266

Gnomad EAS AF: 0.612

Gnomad SAS AF: 0.541

Gnomad FIN AF: 0.257

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.186

Gnomad OTH AF: 0.259

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

GnomAD4 genome AF: 0.262 AC: 39770 AN: 151858 Hom.: 6162 Cov.: 32 AF XY: 0.273 AC XY: 20240 AN XY: 74200

Gnomad4 AFR AF: 0.272

Gnomad4 AMR AF: 0.365

Gnomad4 ASJ AF: 0.266

Gnomad4 EAS AF: 0.613

Gnomad4 SAS AF: 0.541

Gnomad4 FIN AF: 0.257

Gnomad4 NFE AF: 0.186

Gnomad4 OTH AF: 0.268

Alfa AF: 0.206 Hom.: 5300

Bravo AF: 0.266

Asia WGS AF: 0.580 AC: 2007 AN: 3466

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.26
DANN	Benign	0.40

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: rs4618569; hg19: chr6-30855251;