7-7373261-T-A

Variant summary

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

The NM_001037763.3(COL28A1):c.2645A>T(p.Gln882Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00394 in 1,614,184 control chromosomes in the GnomAD database, including 242 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.022 (140 hom., cov: 32)
  • Exomes 𝑓: 0.0021 (102 hom.)
• Consequence: COL28A1 NM_001037763.3 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 4.13

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]

LOC107986764 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.002996266).
• BP6: Variant 7-7373261-T-A is Benign according to our data. Variant chr7-7373261-T-A is described in ClinVar as [Benign]. Clinvar id is 776204.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0735 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL28A1	NM_001037763.3	c.2645A>T	p.Gln882Leu	missense_variant	32/35	ENST00000399429.8
LOC107986764	XR_002956539.2	n.442-3300T>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL28A1	ENST00000399429.8	c.2645A>T	p.Gln882Leu	missense_variant	32/35	1	NM_001037763.3	P1

Frequencies

GnomAD3 genomes AF: 0.0216 AC: 3286 AN: 152172 Hom.: 140 Cov.: 32

Gnomad AFR AF: 0.0758

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00628

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000265

Gnomad OTH AF: 0.0134

GnomAD3 exomes AF: 0.00527 AC: 1316 AN: 249526 Hom.: 42 AF XY: 0.00403 AC XY: 545 AN XY: 135376

Gnomad AFR exome AF: 0.0750

Gnomad AMR exome AF: 0.00313

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000556

Gnomad SAS exome AF: 0.0000654

Gnomad FIN exome AF: 0.0000464

Gnomad NFE exome AF: 0.000221

Gnomad OTH exome AF: 0.00281

GnomAD4 exome AF: 0.00210 AC: 3076 AN: 1461894 Hom.: 102 Cov.: 32 AF XY: 0.00180 AC XY: 1308 AN XY: 727248

Gnomad4 AFR exome AF: 0.0747

Gnomad4 AMR exome AF: 0.00380

Gnomad4 ASJ exome AF: 0.0000383

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000944

Gnomad4 OTH exome AF: 0.00445

GnomAD4 genome AF: 0.0216 AC: 3290 AN: 152290 Hom.: 140 Cov.: 32 AF XY: 0.0204 AC XY: 1519 AN XY: 74468

Gnomad4 AFR AF: 0.0758

Gnomad4 AMR AF: 0.00621

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000265

Gnomad4 OTH AF: 0.0132

Alfa AF: 0.00325 Hom.: 14

Bravo AF: 0.0232

ESP6500AA AF: 0.0659 AC: 266

ESP6500EA AF: 0.000239 AC: 2

ExAC AF: 0.00651 AC: 787

Asia WGS AF: 0.00433 AC: 15 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.000119

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

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.26
Cadd	Benign	22
Dann	Uncertain	0.99
DEOGEN2	Benign	0.038	T
Eigen	Benign	-0.13
Eigen_PC	Benign	-0.0034
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.59	T
MetaRNN	Benign	0.0030	T
MetaSVM	Benign	-0.83	T
MutationAssessor	Benign	1.7	L
MutationTaster	Benign	0.73	N
PrimateAI	Benign	0.31	T
PROVEAN	Uncertain	-2.5	N
REVEL	Uncertain	0.31
Sift	Benign	0.12	T
Sift4G	Uncertain	0.035	D
Polyphen		0.10	B
Vest4		0.35
MVP		0.41
MPC		0.031
ClinPred		0.027	T
GERP RS		4.3
Varity_R		0.18
gMVP		0.53

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: rs61745696; hg19: chr7-7412892;