6-69879738-G-C

Variant summary

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

The ENST00000478620.2(COL19A1):c.171G>C(p.Leu57Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.194 in 1,258,860 control chromosomes in the GnomAD database, including 24,646 homozygotes. In-silico tool predicts a benign outcome for this variant. 8/9 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.17 (2392 hom., cov: 32)
  • Exomes 𝑓: 0.20 (22254 hom.)
• Consequence: COL19A1 ENST00000478620.2 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.00700

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 (MetaRNN=0.0014814734).
• BP6: Variant 6-69879738-G-C is Benign according to our data. Variant chr6-69879738-G-C is described in ClinVar as [Benign]. Clinvar id is 1232931.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.234 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL19A1	NM_001858.6	c.91+80G>C		intron_variant		ENST00000620364.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL19A1	ENST00000478620.2	c.171G>C	p.Leu57Phe	missense_variant	2/2	1
COL19A1	ENST00000620364.5	c.91+80G>C		intron_variant		1	NM_001858.6	P1
COL19A1	ENST00000476656.1	n.212+80G>C		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.170 AC: 25802 AN: 151988 Hom.: 2381 Cov.: 32

Gnomad AFR AF: 0.111

Gnomad AMI AF: 0.172

Gnomad AMR AF: 0.227

Gnomad ASJ AF: 0.118

Gnomad EAS AF: 0.245

Gnomad SAS AF: 0.244

Gnomad FIN AF: 0.181

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.183

Gnomad OTH AF: 0.173

GnomAD4 exome AF: 0.198 AC: 218654 AN: 1106754 Hom.: 22254 Cov.: 14 AF XY: 0.198 AC XY: 110998 AN XY: 560828

Gnomad4 AFR exome AF: 0.109

Gnomad4 AMR exome AF: 0.236

Gnomad4 ASJ exome AF: 0.113

Gnomad4 EAS exome AF: 0.238

Gnomad4 SAS exome AF: 0.237

Gnomad4 FIN exome AF: 0.189

Gnomad4 NFE exome AF: 0.197

Gnomad4 OTH exome AF: 0.190

GnomAD4 genome AF: 0.170 AC: 25835 AN: 152106 Hom.: 2392 Cov.: 32 AF XY: 0.172 AC XY: 12826 AN XY: 74354

Gnomad4 AFR AF: 0.110

Gnomad4 AMR AF: 0.227

Gnomad4 ASJ AF: 0.118

Gnomad4 EAS AF: 0.245

Gnomad4 SAS AF: 0.244

Gnomad4 FIN AF: 0.181

Gnomad4 NFE AF: 0.183

Gnomad4 OTH AF: 0.182

Alfa AF: 0.173 Hom.: 315

Bravo AF: 0.170

TwinsUK AF: 0.199 AC: 737

ALSPAC AF: 0.198 AC: 762

Asia WGS AF: 0.261 AC: 907 AN: 3478

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_addAF	Benign	-0.71	T
BayesDel_noAF	Benign	-0.65
Cadd	Benign	10
Dann	Benign	0.80
FATHMM_MKL	Benign	0.27	N
LIST_S2	Benign	0.24	T
MetaRNN	Benign	0.0015	T
MutationTaster	Benign	1.0	P
Vest4		0.11
MVP		0.62
GERP RS		0.82

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: rs6919210; hg19: chr6-70589630; COSMIC: COSV59591803;