6-56281762-T-C

Variant names:

• chr6-56281762-T-C
• rs2397214
• ENST00000370819.5:c.-38-99106A>G

Variant summary

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

The NM_001318752.2(COL21A1):​c.-38-99106A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.506 in 151,932 control chromosomes in the GnomAD database, including 20,714 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 0.51 (20714 hom., cov: 31)
• Consequence: COL21A1 NM_001318752.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.573

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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.833 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL21A1	NM_001318752.2	c.-38-99106A>G		intron_variant	Intron 1 of 28		NP_001305681.1
COL21A1	XM_011514924.3	c.-38-99106A>G		intron_variant	Intron 1 of 29		XP_011513226.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL21A1	ENST00000370819.5	c.-38-99106A>G		intron_variant	Intron 1 of 28	1		ENSP00000359855.1

Frequencies

GnomAD3 genomes AF: 0.506 AC: 76826 AN: 151814 Hom.: 20687 Cov.: 31

Gnomad AFR AF: 0.349

Gnomad AMI AF: 0.697

Gnomad AMR AF: 0.683

Gnomad ASJ AF: 0.567

Gnomad EAS AF: 0.854

Gnomad SAS AF: 0.686

Gnomad FIN AF: 0.469

Gnomad MID AF: 0.598

Gnomad NFE AF: 0.520

Gnomad OTH AF: 0.570

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

GnomAD4 genome AF: 0.506 AC: 76897 AN: 151932 Hom.: 20714 Cov.: 31 AF XY: 0.515 AC XY: 38238 AN XY: 74254

Gnomad4 AFR AF: 0.349

Gnomad4 AMR AF: 0.684

Gnomad4 ASJ AF: 0.567

Gnomad4 EAS AF: 0.854

Gnomad4 SAS AF: 0.687

Gnomad4 FIN AF: 0.469

Gnomad4 NFE AF: 0.520

Gnomad4 OTH AF: 0.575

Alfa AF: 0.519 Hom.: 3500

Bravo AF: 0.517

Asia WGS AF: 0.761 AC: 2645 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	1.4
DANN	Benign	0.50

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2397214; hg19: chr6-56146560;