rs1925166

Positions:

• chr6-56128447-T-C

Variant summary

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

The NM_030820.4(COL21A1):​c.1543-2298A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.567 in 152,010 control chromosomes in the GnomAD database, including 24,739 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 0.57 (24739 hom., cov: 31)
• Consequence: COL21A1 NM_030820.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.157

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.768 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL21A1	NM_030820.4	c.1543-2298A>G		intron_variant		ENST00000244728.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL21A1	ENST00000244728.10	c.1543-2298A>G		intron_variant		1	NM_030820.4	A1
COL21A1	ENST00000370819.5	c.1534-2298A>G		intron_variant		1		P4
COL21A1	ENST00000456983.1	c.234-2298A>G		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.567 AC: 86100 AN: 151892 Hom.: 24731 Cov.: 31

Gnomad AFR AF: 0.607

Gnomad AMI AF: 0.343

Gnomad AMR AF: 0.496

Gnomad ASJ AF: 0.550

Gnomad EAS AF: 0.788

Gnomad SAS AF: 0.582

Gnomad FIN AF: 0.534

Gnomad MID AF: 0.484

Gnomad NFE AF: 0.550

Gnomad OTH AF: 0.555

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

GnomAD4 genome AF: 0.567 AC: 86155 AN: 152010 Hom.: 24739 Cov.: 31 AF XY: 0.566 AC XY: 42029 AN XY: 74304

Gnomad4 AFR AF: 0.607

Gnomad4 AMR AF: 0.497

Gnomad4 ASJ AF: 0.550

Gnomad4 EAS AF: 0.788

Gnomad4 SAS AF: 0.583

Gnomad4 FIN AF: 0.534

Gnomad4 NFE AF: 0.550

Gnomad4 OTH AF: 0.552

Alfa AF: 0.546 Hom.: 29401

Bravo AF: 0.568

Asia WGS AF: 0.663 AC: 2301 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	5.3
DANN	Benign	0.54

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: rs1925166; hg19: chr6-55993245;