rs17574269

Variant names:

• chr6-117494965-A-G
• rs17574269
• NM_001366458.2:c.113-8802A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001366458.2(DCBLD1):​c.113-8802A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0306 in 152,284 control chromosomes in the GnomAD database, including 83 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 0.031 (83 hom., cov: 32)
  • Exomes 𝑓: 0.10 (0 hom.)
• Consequence: DCBLD1 NM_001366458.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.171
• Publications: 5 publications found

Genes affected

DCBLD1 (HGNC:21479): (discoidin, CUB and LCCL domain containing 1) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000282218 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0306 (4652/152264) while in subpopulation NFE AF = 0.0375 (2552/68024). AF 95% confidence interval is 0.0363. There are 83 homozygotes in GnomAd4. There are 2197 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 83 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001366458.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DCBLD1	NM_001366458.2	MANE Select	c.113-8802A>G		intron	N/A	NP_001353387.1
	DCBLD1	NM_173674.3		c.113-8802A>G		intron	N/A	NP_775945.1
	DCBLD1	NM_001366459.2		c.113-8802A>G		intron	N/A	NP_001353388.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DCBLD1	ENST00000338728.10	TSL:5 MANE Select	c.113-8802A>G		intron	N/A	ENSP00000342422.6
	DCBLD1	ENST00000296955.12	TSL:1	c.113-8802A>G		intron	N/A	ENSP00000296955.8
	ENSG00000282218	ENST00000467125.1	TSL:2	c.547+71889T>C		intron	N/A	ENSP00000487717.1

Frequencies

GnomAD3 genomes AF: 0.0306 AC: 4654 AN: 152146 Hom.: 83 Cov.: 32

Gnomad AFR AF: 0.0258

Gnomad AMI AF: 0.0890

Gnomad AMR AF: 0.0189

Gnomad ASJ AF: 0.0187

Gnomad EAS AF: 0.0254

Gnomad SAS AF: 0.0135

Gnomad FIN AF: 0.0302

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0375

Gnomad OTH AF: 0.0330

GnomAD4 exome AF: 0.100 AC: 2 AN: 20 Hom.: 0 AF XY: 0.125 AC XY: 1 AN XY: 8

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.111 AC: 2 AN: 18

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.0306 AC: 4652 AN: 152264 Hom.: 83 Cov.: 32 AF XY: 0.0295 AC XY: 2197 AN XY: 74456

African (AFR) AF: 0.0258 AC: 1071 AN: 41528

American (AMR) AF: 0.0189 AC: 289 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0187 AC: 65 AN: 3470

East Asian (EAS) AF: 0.0255 AC: 132 AN: 5186

South Asian (SAS) AF: 0.0128 AC: 62 AN: 4826

European-Finnish (FIN) AF: 0.0302 AC: 321 AN: 10616

Middle Eastern (MID) AF: 0.0306 AC: 9 AN: 294

European-Non Finnish (NFE) AF: 0.0375 AC: 2552 AN: 68024

Other (OTH) AF: 0.0331 AC: 70 AN: 2114

Alfa AF: 0.0344 Hom.: 195

Bravo AF: 0.0301

Asia WGS AF: 0.0190 AC: 66 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.7
DANN	Benign	0.66
PhyloP100		0.17
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs17574269; hg19: chr6-117816128;