Variant chr7-7370807-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001037763.3(COL28A1):c.2984C>T(p.Ser995Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,248 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

COL28A1
NM_001037763.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.73

Variant links:

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]

COL28A1 links:

LOC107986764 (HGNC:):

LOC107986764 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.050564617).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COL28A1	NM_001037763.3 linkuse as main transcript	c.2984C>T	p.Ser995Leu	missense_variant	33/35	ENST00000399429.8	NP_001032852.2
LOC107986764	XR_002956539.2 linkuse as main transcript	n.442-5754G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COL28A1	ENST00000399429.8 linkuse as main transcript	c.2984C>T	p.Ser995Leu	missense_variant	33/35	1	NM_001037763.3	ENSP00000382356	P1	Q2UY09-1
COL28A1	ENST00000430711.5 linkuse as main transcript	c.35C>T	p.Ser12Leu	missense_variant, NMD_transcript_variant	1/4	5		ENSP00000413093

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000802

AC:

AN:

249418

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135312

show subpopulations

Gnomad AFR exome

AF:

0.0000646

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000883

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1461248

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726962

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.00e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000264

ExAC

AF:

0.0000166

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 15, 2023

The c.2984C>T (p.S995L) alteration is located in exon 33 (coding exon 32) of the COL28A1 gene. This alteration results from a C to T substitution at nucleotide position 2984, causing the serine (S) at amino acid position 995 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.075

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.31

CADD

Benign

DANN

Benign

0.70

DEOGEN2

Benign

0.0043

Eigen

Benign

-0.99

Eigen_PC

Benign

-0.97

FATHMM_MKL

Benign

0.098

LIST_S2

Benign

0.81

M_CAP

Benign

0.015

MetaRNN

Benign

0.051

MetaSVM

Benign

-0.74

MutationAssessor

Benign

0.55

MutationTaster

Benign

1.0

PrimateAI

Benign

0.31

PROVEAN

Benign

0.13

REVEL

Benign

0.10

Sift

Benign

0.34

Sift4G

Benign

0.72

Polyphen

0.013

Vest4

0.27

MutPred

0.31

Gain of sheet (P = 0.0101);

MVP

0.19

MPC

0.028

ClinPred

0.042

GERP RS

2.6

Varity_R

0.043

gMVP

0.12

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over