6-69932768-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.667-15C>T variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.116 in 1,514,458 control chromosomes in the GnomAD database, including 11,236 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.11 (978 hom., cov: 32)
  • Exomes 𝑓: 0.12 (10258 hom.)
• Consequence: COL19A1 NM_001858.6 splice_polypyrimidine_tract, intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.504

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=-0.85).
• BP6: Variant 6-69932768-C-T is Benign according to our data. Variant chr6-69932768-C-T is described in ClinVar as [Benign]. Clinvar id is 1174254.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.123 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL19A1	NM_001858.6	c.667-15C>T		splice_polypyrimidine_tract_variant, intron_variant		ENST00000620364.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL19A1	ENST00000620364.5	c.667-15C>T		splice_polypyrimidine_tract_variant, intron_variant		1	NM_001858.6	P1

Frequencies

GnomAD3 genomes AF: 0.108 AC: 16349 AN: 151930 Hom.: 977 Cov.: 32

Gnomad AFR AF: 0.0956

Gnomad AMI AF: 0.123

Gnomad AMR AF: 0.0921

Gnomad ASJ AF: 0.208

Gnomad EAS AF: 0.00115

Gnomad SAS AF: 0.0959

Gnomad FIN AF: 0.0831

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.125

Gnomad OTH AF: 0.125

GnomAD3 exomes AF: 0.101 AC: 22983 AN: 227790 Hom.: 1448 AF XY: 0.104 AC XY: 12840 AN XY: 123658

Gnomad AFR exome AF: 0.0909

Gnomad AMR exome AF: 0.0670

Gnomad ASJ exome AF: 0.204

Gnomad EAS exome AF: 0.000476

Gnomad SAS exome AF: 0.0990

Gnomad FIN exome AF: 0.0816

Gnomad NFE exome AF: 0.123

Gnomad OTH exome AF: 0.119

GnomAD4 exome AF: 0.117 AC: 159333 AN: 1362410 Hom.: 10258 Cov.: 19 AF XY: 0.117 AC XY: 79618 AN XY: 681488

Gnomad4 AFR exome AF: 0.0953

Gnomad4 AMR exome AF: 0.0718

Gnomad4 ASJ exome AF: 0.200

Gnomad4 EAS exome AF: 0.000472

Gnomad4 SAS exome AF: 0.100

Gnomad4 FIN exome AF: 0.0837

Gnomad4 NFE exome AF: 0.124

Gnomad4 OTH exome AF: 0.118

GnomAD4 genome AF: 0.108 AC: 16367 AN: 152048 Hom.: 978 Cov.: 32 AF XY: 0.104 AC XY: 7718 AN XY: 74314

Gnomad4 AFR AF: 0.0958

Gnomad4 AMR AF: 0.0919

Gnomad4 ASJ AF: 0.208

Gnomad4 EAS AF: 0.00116

Gnomad4 SAS AF: 0.0953

Gnomad4 FIN AF: 0.0831

Gnomad4 NFE AF: 0.125

Gnomad4 OTH AF: 0.124

Alfa AF: 0.124 Hom.: 269

Bravo AF: 0.108

Asia WGS AF: 0.0450 AC: 158 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

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	6.6
Dann	Benign	0.39

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: rs2345783; hg19: chr6-70642660;