rs12196860

Positions:

• chr6-56085576-G-A

Variant summary

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

The NM_030820.4(COL21A1):​c.1813-8003C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.152 in 151,922 control chromosomes in the GnomAD database, including 1,788 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 0.15 (1788 hom., cov: 32)
• Consequence: COL21A1 NM_030820.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.507

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=-1.04).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.169 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COL21A1	NM_030820.4	c.1813-8003C>T		intron_variant		ENST00000244728.10	NP_110447.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COL21A1	ENST00000244728.10	c.1813-8003C>T		intron_variant		1	NM_030820.4	ENSP00000244728	A1
COL21A1	ENST00000370819.5	c.1804-8003C>T		intron_variant		1		ENSP00000359855	P4
COL21A1	ENST00000488912.5	c.205-7388C>T		intron_variant, NMD_transcript_variant		1		ENSP00000433624
COL21A1	ENST00000467045.5	n.165+5921C>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.152 AC: 23067 AN: 151804 Hom.: 1787 Cov.: 32

Gnomad AFR AF: 0.161

Gnomad AMI AF: 0.201

Gnomad AMR AF: 0.175

Gnomad ASJ AF: 0.169

Gnomad EAS AF: 0.0740

Gnomad SAS AF: 0.140

Gnomad FIN AF: 0.155

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.146

Gnomad OTH AF: 0.147

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

GnomAD4 genome AF: 0.152 AC: 23093 AN: 151922 Hom.: 1788 Cov.: 32 AF XY: 0.153 AC XY: 11345 AN XY: 74234

Gnomad4 AFR AF: 0.161

Gnomad4 AMR AF: 0.175

Gnomad4 ASJ AF: 0.169

Gnomad4 EAS AF: 0.0742

Gnomad4 SAS AF: 0.140

Gnomad4 FIN AF: 0.155

Gnomad4 NFE AF: 0.146

Gnomad4 OTH AF: 0.145

Alfa AF: 0.149 Hom.: 820

Bravo AF: 0.151

Asia WGS AF: 0.106 AC: 367 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.6
DANN	Benign	0.24

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: rs12196860; hg19: chr6-55950374;