rs4119564

Variant names:

• chr6-56258960-T-C
• rs4119564
• ENST00000370819.5:c.-38-76304A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001318752.2(COL21A1):​c.-38-76304A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.217 in 152,198 control chromosomes in the GnomAD database, including 4,160 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 0.22 (4160 hom., cov: 32)
• Consequence: COL21A1 NM_001318752.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0190
• Publications: 0 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=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.282 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001318752.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL21A1	NM_001318752.2		c.-38-76304A>G		intron	N/A	NP_001305681.1	Q96P44-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL21A1	ENST00000370819.5	TSL:1	c.-38-76304A>G		intron	N/A	ENSP00000359855.1	Q96P44-3

Frequencies

GnomAD3 genomes AF: 0.217 AC: 33047 AN: 152080 Hom.: 4164 Cov.: 32

Gnomad AFR AF: 0.0974

Gnomad AMI AF: 0.541

Gnomad AMR AF: 0.198

Gnomad ASJ AF: 0.257

Gnomad EAS AF: 0.187

Gnomad SAS AF: 0.216

Gnomad FIN AF: 0.242

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.285

Gnomad OTH AF: 0.257

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

GnomAD4 genome AF: 0.217 AC: 33027 AN: 152198 Hom.: 4160 Cov.: 32 AF XY: 0.216 AC XY: 16052 AN XY: 74408

African (AFR) AF: 0.0971 AC: 4032 AN: 41540

American (AMR) AF: 0.197 AC: 3020 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.257 AC: 891 AN: 3472

East Asian (EAS) AF: 0.187 AC: 966 AN: 5172

South Asian (SAS) AF: 0.216 AC: 1040 AN: 4824

European-Finnish (FIN) AF: 0.242 AC: 2562 AN: 10582

Middle Eastern (MID) AF: 0.269 AC: 79 AN: 294

European-Non Finnish (NFE) AF: 0.285 AC: 19409 AN: 67998

Other (OTH) AF: 0.254 AC: 536 AN: 2112

Alfa AF: 0.262 Hom.: 2777

Bravo AF: 0.208

Asia WGS AF: 0.178 AC: 618 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.1
DANN	Benign	0.86
PhyloP100		-0.019
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs4119564; hg19: chr6-56123758;