NM_001037763.3:c.240A>C

Variant names:

• chr7-7531789-T-G
• rs17168526
• NM_001037763.3:c.240A>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001037763.3(COL28A1):​c.240A>C​(p.Gln80His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000131 in 152,198 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. Q80Q) has been classified as Benign.

• Frequency: Genomes: 𝑓 0.000013 (0 hom., cov: 32)
• Consequence: COL28A1 NM_001037763.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.93
• Publications: 4 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.047427416).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001037763.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL28A1	NM_001037763.3	MANE Select	c.240A>C	p.Gln80His	missense	Exon 3 of 35	NP_001032852.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL28A1	ENST00000399429.8	TSL:1 MANE Select	c.240A>C	p.Gln80His	missense	Exon 3 of 35	ENSP00000382356.3

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152198 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 27

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152198 Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2 AN XY: 74372

African (AFR) AF: 0.0000483 AC: 2 AN: 41436

American (AMR) AF: 0.00 AC: 0 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5202

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68036

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.00 Hom.: 136

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	0.059
DANN	Benign	0.89
DEOGEN2	Benign	0.068	T
Eigen	Benign	-1.8
Eigen_PC	Benign	-2.0
FATHMM_MKL	Benign	0.029	N
LIST_S2	Benign	0.60	T
M_CAP	Benign	0.024	T
MetaRNN	Benign	0.047	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.81	L
PhyloP100		-1.9
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.19
Sift	Benign	0.11	T
Sift4G	Benign	0.15	T
Polyphen		0.016	B
Vest4		0.093
MutPred		0.43		Loss of disorder (P = 0.1206)
MVP		0.085
MPC		0.23
ClinPred		0.077	T
GERP RS		-8.4
Varity_R		0.15
gMVP		0.24
Mutation Taster		=76/24	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs17168526; hg19: chr7-7571420;