6-56156414-C-T

Position:

• chr6-56156414-C-T

Variant summary

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

The NM_030820.4(COL21A1):​c.1434+473G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.742 in 152,074 control chromosomes in the GnomAD database, including 42,432 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 0.74 (42432 hom., cov: 31)
• Consequence: COL21A1 NM_030820.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0210

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]

COL21A1 (HGNC:):

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 = 0.843 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COL21A1	NM_030820.4	c.1434+473G>A		intron_variant		ENST00000244728.10	NP_110447.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COL21A1	ENST00000244728.10	c.1434+473G>A		intron_variant		1	NM_030820.4	ENSP00000244728.5
COL21A1	ENST00000370819.5	c.1425+473G>A		intron_variant		1		ENSP00000359855.1
COL21A1	ENST00000456983.1	c.123+8009G>A		intron_variant		3		ENSP00000390958.1

Frequencies

GnomAD3 genomes AF: 0.742 AC: 112774 AN: 151956 Hom.: 42403 Cov.: 31

Gnomad AFR AF: 0.851

Gnomad AMI AF: 0.543

Gnomad AMR AF: 0.678

Gnomad ASJ AF: 0.714

Gnomad EAS AF: 0.863

Gnomad SAS AF: 0.727

Gnomad FIN AF: 0.690

Gnomad MID AF: 0.691

Gnomad NFE AF: 0.695

Gnomad OTH AF: 0.715

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

GnomAD4 genome AF: 0.742 AC: 112855 AN: 152074 Hom.: 42432 Cov.: 31 AF XY: 0.741 AC XY: 55093 AN XY: 74328

Gnomad4 AFR AF: 0.851

Gnomad4 AMR AF: 0.678

Gnomad4 ASJ AF: 0.714

Gnomad4 EAS AF: 0.864

Gnomad4 SAS AF: 0.727

Gnomad4 FIN AF: 0.690

Gnomad4 NFE AF: 0.695

Gnomad4 OTH AF: 0.711

Alfa AF: 0.708 Hom.: 19079

Bravo AF: 0.745

Asia WGS AF: 0.780 AC: 2710 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	1.7
DANN	Benign	0.61

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: rs1925179; hg19: chr6-56021212;