6-56349494-G-A

Position:

• chr6-56349494-G-A

Variant summary

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

The ENST00000370819.5(COL21A1):​c.-39+44477C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.357 in 152,030 control chromosomes in the GnomAD database, including 10,494 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 0.36 (10494 hom., cov: 33)
• Consequence: COL21A1 ENST00000370819.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.268

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 = 0.703 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COL21A1	NM_001318752.2	c.-39+44477C>T		intron_variant			NP_001305681.1
COL21A1	XM_011514924.3	c.-39+44477C>T		intron_variant			XP_011513226.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COL21A1	ENST00000370819.5	c.-39+44477C>T		intron_variant		1		ENSP00000359855	P4

Frequencies

GnomAD3 genomes AF: 0.357 AC: 54172 AN: 151912 Hom.: 10458 Cov.: 33

Gnomad AFR AF: 0.385

Gnomad AMI AF: 0.190

Gnomad AMR AF: 0.476

Gnomad ASJ AF: 0.302

Gnomad EAS AF: 0.721

Gnomad SAS AF: 0.420

Gnomad FIN AF: 0.277

Gnomad MID AF: 0.296

Gnomad NFE AF: 0.298

Gnomad OTH AF: 0.353

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

GnomAD4 genome AF: 0.357 AC: 54268 AN: 152030 Hom.: 10494 Cov.: 33 AF XY: 0.361 AC XY: 26800 AN XY: 74300

Gnomad4 AFR AF: 0.385

Gnomad4 AMR AF: 0.476

Gnomad4 ASJ AF: 0.302

Gnomad4 EAS AF: 0.722

Gnomad4 SAS AF: 0.420

Gnomad4 FIN AF: 0.277

Gnomad4 NFE AF: 0.298

Gnomad4 OTH AF: 0.360

Alfa AF: 0.346 Hom.: 1642

Bravo AF: 0.374

Asia WGS AF: 0.560 AC: 1945 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.8
DANN	Benign	0.38

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs9296842; hg19: chr6-56214292;