6-69933126-A-G

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.747+263A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.288 in 151,948 control chromosomes in the GnomAD database, including 7,809 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.29 (7809 hom., cov: 32)
• Consequence: COL19A1 NM_001858.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.92

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=-0.78).
• BP6: Variant 6-69933126-A-G is Benign according to our data. Variant chr6-69933126-A-G is described in ClinVar as [Benign]. Clinvar id is 1288496.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.384 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL19A1	NM_001858.6	c.747+263A>G		intron_variant		ENST00000620364.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL19A1	ENST00000620364.5	c.747+263A>G		intron_variant		1	NM_001858.6	P1

Frequencies

GnomAD3 genomes AF: 0.289 AC: 43843 AN: 151830 Hom.: 7812 Cov.: 32

Gnomad AFR AF: 0.0727

Gnomad AMI AF: 0.563

Gnomad AMR AF: 0.293

Gnomad ASJ AF: 0.338

Gnomad EAS AF: 0.340

Gnomad SAS AF: 0.303

Gnomad FIN AF: 0.426

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.388

Gnomad OTH AF: 0.286

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

GnomAD4 genome AF: 0.288 AC: 43834 AN: 151948 Hom.: 7809 Cov.: 32 AF XY: 0.288 AC XY: 21405 AN XY: 74248

Gnomad4 AFR AF: 0.0725

Gnomad4 AMR AF: 0.292

Gnomad4 ASJ AF: 0.338

Gnomad4 EAS AF: 0.339

Gnomad4 SAS AF: 0.304

Gnomad4 FIN AF: 0.426

Gnomad4 NFE AF: 0.388

Gnomad4 OTH AF: 0.284

Alfa AF: 0.355 Hom.: 13508

Bravo AF: 0.269

Asia WGS AF: 0.286 AC: 995 AN: 3476

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	-0.78
Cadd	Benign	11
Dann	Benign	0.84

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: rs2273428; hg19: chr6-70643018;