chr6-56242467-A-T

Position:

• chr6-56242467-A-T

Variant summary

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

The NM_030820.4(COL21A1):​c.-39+4920T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.462 in 151,968 control chromosomes in the GnomAD database, including 17,760 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 0.46 (17760 hom., cov: 32)
• Consequence: COL21A1 NM_030820.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.23

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=-0.59).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.647 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COL21A1	NM_030820.4	c.-39+4920T>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.-39+4920T>A		intron_variant		1	NM_030820.4	ENSP00000244728.5
COL21A1	ENST00000370819.5	c.-38-59811T>A		intron_variant		1		ENSP00000359855.1
COL21A1	ENST00000370817.3	c.-165+4920T>A		intron_variant		3		ENSP00000359853.3

Frequencies

GnomAD3 genomes AF: 0.462 AC: 70171 AN: 151850 Hom.: 17743 Cov.: 32

Gnomad AFR AF: 0.654

Gnomad AMI AF: 0.133

Gnomad AMR AF: 0.364

Gnomad ASJ AF: 0.409

Gnomad EAS AF: 0.0956

Gnomad SAS AF: 0.299

Gnomad FIN AF: 0.453

Gnomad MID AF: 0.426

Gnomad NFE AF: 0.418

Gnomad OTH AF: 0.399

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

GnomAD4 genome AF: 0.462 AC: 70221 AN: 151968 Hom.: 17760 Cov.: 32 AF XY: 0.457 AC XY: 33941 AN XY: 74276

Gnomad4 AFR AF: 0.654

Gnomad4 AMR AF: 0.363

Gnomad4 ASJ AF: 0.409

Gnomad4 EAS AF: 0.0953

Gnomad4 SAS AF: 0.298

Gnomad4 FIN AF: 0.453

Gnomad4 NFE AF: 0.418

Gnomad4 OTH AF: 0.395

Alfa AF: 0.299 Hom.: 673

Bravo AF: 0.459

Asia WGS AF: 0.225 AC: 787 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	15
DANN	Benign	0.78

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: rs1925156; hg19: chr6-56107265;