6-30880476-T-C

Variant names:

• chr6-30880476-T-C
• rs7756521
• ENST00000505066.5:c.-43+3917T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000505066.5(DDR1):​c.-43+3917T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.261 in 152,060 control chromosomes in the GnomAD database, including 6,151 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 (6151 hom., cov: 31)
• Consequence: DDR1 ENST00000505066.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0530
• Publications: 53 publications found

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]

DDR1 Gene-Disease associations (from GenCC):

• chondrodysplasia

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.594 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DDR1	ENST00000505066.5	c.-43+3917T>C		intron_variant	Intron 1 of 3	4		ENSP00000421189.1
DDR1	ENST00000502955.5	c.-270-422T>C		intron_variant	Intron 1 of 3	4		ENSP00000424346.1

Frequencies

GnomAD3 genomes AF: 0.261 AC: 39705 AN: 151942 Hom.: 6136 Cov.: 31

Gnomad AFR AF: 0.272

Gnomad AMI AF: 0.300

Gnomad AMR AF: 0.364

Gnomad ASJ AF: 0.266

Gnomad EAS AF: 0.611

Gnomad SAS AF: 0.540

Gnomad FIN AF: 0.256

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.186

Gnomad OTH AF: 0.257

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

GnomAD4 genome AF: 0.261 AC: 39744 AN: 152060 Hom.: 6151 Cov.: 31 AF XY: 0.272 AC XY: 20216 AN XY: 74316

African (AFR) AF: 0.272 AC: 11264 AN: 41478

American (AMR) AF: 0.365 AC: 5569 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.266 AC: 923 AN: 3468

East Asian (EAS) AF: 0.612 AC: 3155 AN: 5158

South Asian (SAS) AF: 0.539 AC: 2599 AN: 4818

European-Finnish (FIN) AF: 0.256 AC: 2704 AN: 10568

Middle Eastern (MID) AF: 0.224 AC: 66 AN: 294

European-Non Finnish (NFE) AF: 0.186 AC: 12631 AN: 67986

Other (OTH) AF: 0.266 AC: 560 AN: 2108

Alfa AF: 0.221 Hom.: 12651

Bravo AF: 0.266

Asia WGS AF: 0.582 AC: 2019 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	11
DANN	Benign	0.68
PhyloP100		0.053
PromoterAI		0.0088	Neutral

Splicing

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

Other links and lift over

dbSNP: rs7756521; hg19: chr6-30848253;