ENST00000370819.5:c.-39+48005G>A

Variant names:

• chr6-56345966-C-T
• rs16887812
• ENST00000370819.5:c.-39+48005G>A

Variant summary

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

The ENST00000370819.5(COL21A1):​c.-39+48005G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.333 in 152,100 control chromosomes in the GnomAD database, including 8,631 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 0.33 (8631 hom., cov: 33)
• Consequence: COL21A1 ENST00000370819.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.277
• Publications: 9 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=-0.55).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.359 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000370819.5. 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.-39+48005G>A		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.-39+48005G>A		intron	N/A	ENSP00000359855.1	Q96P44-3

Frequencies

GnomAD3 genomes AF: 0.334 AC: 50694 AN: 151982 Hom.: 8637 Cov.: 33

Gnomad AFR AF: 0.305

Gnomad AMI AF: 0.581

Gnomad AMR AF: 0.300

Gnomad ASJ AF: 0.335

Gnomad EAS AF: 0.164

Gnomad SAS AF: 0.374

Gnomad FIN AF: 0.350

Gnomad MID AF: 0.395

Gnomad NFE AF: 0.362

Gnomad OTH AF: 0.328

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

GnomAD4 genome AF: 0.333 AC: 50694 AN: 152100 Hom.: 8631 Cov.: 33 AF XY: 0.335 AC XY: 24895 AN XY: 74342

African (AFR) AF: 0.305 AC: 12648 AN: 41484

American (AMR) AF: 0.299 AC: 4573 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.335 AC: 1163 AN: 3472

East Asian (EAS) AF: 0.164 AC: 848 AN: 5184

South Asian (SAS) AF: 0.374 AC: 1799 AN: 4816

European-Finnish (FIN) AF: 0.350 AC: 3699 AN: 10566

Middle Eastern (MID) AF: 0.390 AC: 114 AN: 292

European-Non Finnish (NFE) AF: 0.362 AC: 24636 AN: 67982

Other (OTH) AF: 0.325 AC: 685 AN: 2110

Alfa AF: 0.341 Hom.: 3516

Bravo AF: 0.324

Asia WGS AF: 0.264 AC: 918 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	6.5
DANN	Benign	0.72
PhyloP100		0.28
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: rs16887812; hg19: chr6-56210764;