rs17168526

chr7-7531789-T-Cchr7-7531789-T-G

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_001037763.3(COL28A1):c.240A>G(p.Gln80=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00426 in 1,605,212 control chromosomes in the GnomAD database, including 243 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.022 (146 hom., cov: 32)
  • Exomes 𝑓: 0.0024 (97 hom.)
• Consequence: COL28A1 NM_001037763.3 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.93

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 -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BP6: Variant 7-7531789-T-C is Benign according to our data. Variant chr7-7531789-T-C is described in ClinVar as [Benign]. Clinvar id is 776205.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-1.93 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0739 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL28A1	NM_001037763.3	c.240A>G	p.Gln80=	synonymous_variant	3/35	ENST00000399429.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL28A1	ENST00000399429.8	c.240A>G	p.Gln80=	synonymous_variant	3/35	1	NM_001037763.3	P1

Frequencies

GnomAD3 genomes AF: 0.0219 AC: 3329 AN: 152186 Hom.: 147 Cov.: 32

Gnomad AFR AF: 0.0761

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00779

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.0000941

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000309

Gnomad OTH AF: 0.0143

GnomAD3 exomes AF: 0.00573 AC: 1426 AN: 248946 Hom.: 45 AF XY: 0.00455 AC XY: 614 AN XY: 135046

Gnomad AFR exome AF: 0.0785

Gnomad AMR exome AF: 0.00411

Gnomad ASJ exome AF: 0.000299

Gnomad EAS exome AF: 0.000111

Gnomad SAS exome AF: 0.000392

Gnomad FIN exome AF: 0.000186

Gnomad NFE exome AF: 0.000293

Gnomad OTH exome AF: 0.00248

GnomAD4 exome AF: 0.00240 AC: 3494 AN: 1452906 Hom.: 97 Cov.: 27 AF XY: 0.00211 AC XY: 1524 AN XY: 723584

Gnomad4 AFR exome AF: 0.0783

Gnomad4 AMR exome AF: 0.00467

Gnomad4 ASJ exome AF: 0.000422

Gnomad4 EAS exome AF: 0.000101

Gnomad4 SAS exome AF: 0.000314

Gnomad4 FIN exome AF: 0.000131

Gnomad4 NFE exome AF: 0.000251

Gnomad4 OTH exome AF: 0.00526

GnomAD4 genome AF: 0.0219 AC: 3338 AN: 152306 Hom.: 146 Cov.: 32 AF XY: 0.0217 AC XY: 1616 AN XY: 74498

Gnomad4 AFR AF: 0.0761

Gnomad4 AMR AF: 0.00778

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000621

Gnomad4 FIN AF: 0.0000941

Gnomad4 NFE AF: 0.000309

Gnomad4 OTH AF: 0.0142

Alfa AF: 0.00331 Hom.: 41

Bravo AF: 0.0244

Asia WGS AF: 0.00722 AC: 25 AN: 3478

EpiCase AF: 0.000545

EpiControl AF: 0.000178

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	-0.99
Cadd	Benign	0.12
Dann	Benign	0.15

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs17168526; hg19: chr7-7571420;