chr4-108843849-T-C

Position:

• chr4-108843849-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_198721.4(COL25A1):​c.1629+670A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.612 in 151,680 control chromosomes in the GnomAD database, including 28,725 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.61 (28725 hom., cov: 31)
• Consequence: COL25A1 NM_198721.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0650

Genes affected

COL25A1 (HGNC:18603): (collagen type XXV alpha 1 chain) This gene encodes a brain-specific membrane associated collagen. A product of proteolytic processing of the encoded protein, CLAC (collagenous Alzheimer amyloid plaque component), binds to amyloid beta-peptides found in Alzheimer amyloid plaques but CLAC inhibits rather than facilitates amyloid fibril elongation (PMID: 16300410). A study of over-expression of this collagen in mice, however, found changes in pathology and behavior suggesting that the encoded protein may promote amyloid plaque formation (PMID: 19548013). Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2011]

COL25A1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.75 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COL25A1	NM_198721.4	c.1629+670A>G		intron_variant		ENST00000399132.6	NP_942014.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COL25A1	ENST00000399132.6	c.1629+670A>G		intron_variant		5	NM_198721.4	ENSP00000382083.1

Frequencies

GnomAD3 genomes AF: 0.612 AC: 92761 AN: 151568 Hom.: 28706 Cov.: 31

Gnomad AFR AF: 0.531

Gnomad AMI AF: 0.703

Gnomad AMR AF: 0.675

Gnomad ASJ AF: 0.640

Gnomad EAS AF: 0.619

Gnomad SAS AF: 0.770

Gnomad FIN AF: 0.686

Gnomad MID AF: 0.669

Gnomad NFE AF: 0.621

Gnomad OTH AF: 0.631

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.612 AC: 92815 AN: 151680 Hom.: 28725 Cov.: 31 AF XY: 0.618 AC XY: 45782 AN XY: 74090

Gnomad4 AFR AF: 0.531

Gnomad4 AMR AF: 0.675

Gnomad4 ASJ AF: 0.640

Gnomad4 EAS AF: 0.619

Gnomad4 SAS AF: 0.770

Gnomad4 FIN AF: 0.686

Gnomad4 NFE AF: 0.621

Gnomad4 OTH AF: 0.629

Alfa AF: 0.615 Hom.: 5575

Bravo AF: 0.607

Asia WGS AF: 0.685 AC: 2378 AN: 3466

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	3.7
DANN	Benign	0.63

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: rs1452688; hg19: chr4-109765005;