7-7380698-A-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_001037763.3(COL28A1):c.2287-3T>C variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00147 in 1,613,558 control chromosomes in the GnomAD database, including 39 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0081 (23 hom., cov: 32)
  • Exomes 𝑓: 0.00078 (16 hom.)
• Consequence: COL28A1 NM_001037763.3 splice_region, splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.00003917
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.00300

Genes affected

COL28A1 (HGNC:22442): (collagen type XXVIII alpha 1 chain) COL28A1 belongs to a class of collagens containing von Willebrand factor (VWF; MIM 613160) type A (VWFA) domains (Veit et al., 2006 [PubMed 16330543]).[supplied by OMIM, Nov 2010]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 7-7380698-A-G is Benign according to our data. Variant chr7-7380698-A-G is described in ClinVar as [Benign]. Clinvar id is 787848.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00808 (1230/152274) while in subpopulation AFR AF= 0.0284 (1180/41546). AF 95% confidence interval is 0.0271. There are 23 homozygotes in gnomad4. There are 560 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 23 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL28A1	NM_001037763.3	c.2287-3T>C		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000399429.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL28A1	ENST00000399429.8	c.2287-3T>C		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_001037763.3	P1

Frequencies

GnomAD3 genomes AF: 0.00807 AC: 1228 AN: 152156 Hom.: 23 Cov.: 32

Gnomad AFR AF: 0.0284

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00255

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000882

Gnomad OTH AF: 0.00239

GnomAD3 exomes AF: 0.00205 AC: 511 AN: 249486 Hom.: 9 AF XY: 0.00157 AC XY: 212 AN XY: 135356

Gnomad AFR exome AF: 0.0283

Gnomad AMR exome AF: 0.00148

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000883

Gnomad OTH exome AF: 0.00182

GnomAD4 exome AF: 0.000785 AC: 1147 AN: 1461284 Hom.: 16 Cov.: 30 AF XY: 0.000658 AC XY: 478 AN XY: 726980

Gnomad4 AFR exome AF: 0.0274

Gnomad4 AMR exome AF: 0.00197

Gnomad4 ASJ exome AF: 0.0000383

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000232

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000378

Gnomad4 OTH exome AF: 0.00152

GnomAD4 genome AF: 0.00808 AC: 1230 AN: 152274 Hom.: 23 Cov.: 32 AF XY: 0.00752 AC XY: 560 AN XY: 74452

Gnomad4 AFR AF: 0.0284

Gnomad4 AMR AF: 0.00248

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000882

Gnomad4 OTH AF: 0.00237

Alfa AF: 0.00451 Hom.: 6

Bravo AF: 0.00866

Asia WGS AF: 0.00173 AC: 6 AN: 3478

EpiCase AF: 0.00

EpiControl AF: 0.0000593

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

Invitae

Jul 25, 2017

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
Cadd	Benign	17
Dann	Benign	0.52

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000039
SpliceAI score (max)		0.51		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.51		Position offset: 0
DS_DG_spliceai		0.24		Position offset: -38

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs114280533; hg19: chr7-7420329;