chr6-56349494-G-A

Variant names:

• chr6-56349494-G-A
• rs9296842
• ENST00000370819.5:c.-39+44477C>T

Variant summary

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

The NM_001318752.2(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 NM_001318752.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.268
• Publications: 2 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 = 0.703 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.-39+44477C>T		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+44477C>T		intron	N/A	ENSP00000359855.1	Q96P44-3

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

African (AFR) AF: 0.385 AC: 15977 AN: 41472

American (AMR) AF: 0.476 AC: 7278 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.302 AC: 1049 AN: 3468

East Asian (EAS) AF: 0.722 AC: 3731 AN: 5168

South Asian (SAS) AF: 0.420 AC: 2025 AN: 4820

European-Finnish (FIN) AF: 0.277 AC: 2915 AN: 10536

Middle Eastern (MID) AF: 0.298 AC: 87 AN: 292

European-Non Finnish (NFE) AF: 0.298 AC: 20275 AN: 67984

Other (OTH) AF: 0.360 AC: 758 AN: 2104

Alfa AF: 0.348 Hom.: 1715

Bravo AF: 0.374

Asia WGS AF: 0.560 AC: 1945 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.8
DANN	Benign	0.38
PhyloP100		0.27
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: rs9296842; hg19: chr6-56214292;