chr6-56128447-T-C

Variant names:

• chr6-56128447-T-C
• rs1925166
• NM_030820.4:c.1543-2298A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
COL21A1	NM_030820.4	c.1543-2298A>G		intron_variant	Intron 12 of 29	ENST00000244728.10	NP_110447.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL21A1	ENST00000244728.10	c.1543-2298A>G		intron_variant	Intron 12 of 29	1	NM_030820.4	ENSP00000244728.5
COL21A1	ENST00000370819.5	c.1534-2298A>G		intron_variant	Intron 11 of 28	1		ENSP00000359855.1
COL21A1	ENST00000456983.1	c.232-2298A>G		intron_variant	Intron 5 of 6	3		ENSP00000390958.1

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

African (AFR) AF: 0.607 AC: 25144 AN: 41438

American (AMR) AF: 0.497 AC: 7585 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.550 AC: 1908 AN: 3468

East Asian (EAS) AF: 0.788 AC: 4065 AN: 5156

South Asian (SAS) AF: 0.583 AC: 2811 AN: 4824

European-Finnish (FIN) AF: 0.534 AC: 5645 AN: 10580

Middle Eastern (MID) AF: 0.480 AC: 141 AN: 294

European-Non Finnish (NFE) AF: 0.550 AC: 37378 AN: 67954

Other (OTH) AF: 0.552 AC: 1167 AN: 2114

Alfa AF: 0.547 Hom.: 37599

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
PhyloP100		0.16
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1925166; hg19: chr6-55993245;