6-69900391-C-T

Position:

• chr6-69900391-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001858.6(COL19A1):​c.266+53C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0905 in 954,136 control chromosomes in the GnomAD database, including 4,484 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.091 (755 hom., cov: 32)
  • Exomes 𝑓: 0.090 (3729 hom.)
• Consequence: COL19A1 NM_001858.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.194

Genes affected

COL19A1 (HGNC:2196): (collagen type XIX alpha 1 chain) This gene encodes the alpha chain of type XIX collagen, a member of the FACIT collagen family (fibril-associated collagens with interrupted helices). Although the function of this collagen is not known, other members of this collagen family are found in association with fibril-forming collagens such as type I and II, and serve to maintain the integrity of the extracellular matrix. The transcript produced from this gene has an unusually large 3' UTR which has not been completely sequenced. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 6-69900391-C-T is Benign according to our data. Variant chr6-69900391-C-T is described in ClinVar as [Benign]. Clinvar id is 1248940.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.195 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COL19A1	NM_001858.6	c.266+53C>T		intron_variant		ENST00000620364.5	NP_001849.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COL19A1	ENST00000620364.5	c.266+53C>T		intron_variant		1	NM_001858.6	ENSP00000480474	P1

Frequencies

GnomAD3 genomes AF: 0.0913 AC: 13877 AN: 151984 Hom.: 750 Cov.: 32

Gnomad AFR AF: 0.0856

Gnomad AMI AF: 0.0164

Gnomad AMR AF: 0.135

Gnomad ASJ AF: 0.0628

Gnomad EAS AF: 0.205

Gnomad SAS AF: 0.193

Gnomad FIN AF: 0.0765

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0742

Gnomad OTH AF: 0.0857

GnomAD4 exome AF: 0.0903 AC: 72437 AN: 802034 Hom.: 3729 AF XY: 0.0928 AC XY: 37706 AN XY: 406414

Gnomad4 AFR exome AF: 0.0877

Gnomad4 AMR exome AF: 0.142

Gnomad4 ASJ exome AF: 0.0633

Gnomad4 EAS exome AF: 0.187

Gnomad4 SAS exome AF: 0.192

Gnomad4 FIN exome AF: 0.0743

Gnomad4 NFE exome AF: 0.0785

Gnomad4 OTH exome AF: 0.0924

GnomAD4 genome AF: 0.0914 AC: 13908 AN: 152102 Hom.: 755 Cov.: 32 AF XY: 0.0955 AC XY: 7101 AN XY: 74362

Gnomad4 AFR AF: 0.0855

Gnomad4 AMR AF: 0.136

Gnomad4 ASJ AF: 0.0628

Gnomad4 EAS AF: 0.205

Gnomad4 SAS AF: 0.193

Gnomad4 FIN AF: 0.0765

Gnomad4 NFE AF: 0.0742

Gnomad4 OTH AF: 0.0934

Alfa AF: 0.0809 Hom.: 107

Bravo AF: 0.0938

Asia WGS AF: 0.212 AC: 729 AN: 3452

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 18, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	7.5
DANN	Benign	0.51

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: rs9454910; hg19: chr6-70610283;