rs4119564

chr6-56258960-T-C

Variant summary

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

The ENST00000370819.5(COL21A1):c.-38-76304A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.217 in 152,198 control chromosomes in the GnomAD database, including 4,160 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 0.22 (4160 hom., cov: 32)
• Consequence: COL21A1 ENST00000370819.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0190

Genes affected

COL21A1 (HGNC:17025): (collagen type XXI alpha 1 chain) This gene encodes the alpha chain of type XXI collagen, a member of the FACIT (fibril-associated collagens with interrupted helices) collagen family. Type XXI collagen is localized to tissues containing type I collagen and maintains the integrity of the extracellular matrix. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.282 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL21A1	NM_001318752.2	c.-38-76304A>G		intron_variant
COL21A1	XM_011514924.3	c.-38-76304A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL21A1	ENST00000370819.5	c.-38-76304A>G		intron_variant		1		P4

Frequencies

GnomAD3 genomes AF: 0.217 AC: 33047 AN: 152080 Hom.: 4164 Cov.: 32

Gnomad AFR AF: 0.0974

Gnomad AMI AF: 0.541

Gnomad AMR AF: 0.198

Gnomad ASJ AF: 0.257

Gnomad EAS AF: 0.187

Gnomad SAS AF: 0.216

Gnomad FIN AF: 0.242

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.285

Gnomad OTH AF: 0.257

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

GnomAD4 genome AF: 0.217 AC: 33027 AN: 152198 Hom.: 4160 Cov.: 32 AF XY: 0.216 AC XY: 16052 AN XY: 74408

Gnomad4 AFR AF: 0.0971

Gnomad4 AMR AF: 0.197

Gnomad4 ASJ AF: 0.257

Gnomad4 EAS AF: 0.187

Gnomad4 SAS AF: 0.216

Gnomad4 FIN AF: 0.242

Gnomad4 NFE AF: 0.285

Gnomad4 OTH AF: 0.254

Alfa AF: 0.262 Hom.: 2470

Bravo AF: 0.208

Asia WGS AF: 0.178 AC: 618 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	1.1
Dann	Benign	0.86

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4119564; hg19: chr6-56123758;