rs11942576

chr4-108841762-C-Achr4-108841762-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_198721.4(COL25A1):c.1630-41G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.628 in 1,508,322 control chromosomes in the GnomAD database, including 300,132 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in Lovd as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.62 (29461 hom., cov: 31)
  • Exomes 𝑓: 0.63 (270671 hom.)
• Consequence: COL25A1 NM_198721.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.507

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]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 4-108841762-C-A is Benign according to our data. Variant chr4-108841762-C-A is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.755 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL25A1	NM_198721.4	c.1630-41G>T		intron_variant		ENST00000399132.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL25A1	ENST00000399132.6	c.1630-41G>T		intron_variant		5	NM_198721.4

Frequencies

GnomAD3 genomes AF: 0.620 AC: 94082 AN: 151782 Hom.: 29437 Cov.: 31

Gnomad AFR AF: 0.542

Gnomad AMI AF: 0.712

Gnomad AMR AF: 0.684

Gnomad ASJ AF: 0.655

Gnomad EAS AF: 0.651

Gnomad SAS AF: 0.776

Gnomad FIN AF: 0.688

Gnomad MID AF: 0.699

Gnomad NFE AF: 0.625

Gnomad OTH AF: 0.637

GnomAD3 exomes AF: 0.663 AC: 162521 AN: 244972 Hom.: 54379 AF XY: 0.667 AC XY: 88604 AN XY: 132864

Gnomad AFR exome AF: 0.546

Gnomad AMR exome AF: 0.729

Gnomad ASJ exome AF: 0.659

Gnomad EAS exome AF: 0.647

Gnomad SAS exome AF: 0.762

Gnomad FIN exome AF: 0.682

Gnomad NFE exome AF: 0.633

Gnomad OTH exome AF: 0.649

GnomAD4 exome AF: 0.629 AC: 853164 AN: 1356424 Hom.: 270671 Cov.: 20 AF XY: 0.633 AC XY: 431100 AN XY: 680744

Gnomad4 AFR exome AF: 0.540

Gnomad4 AMR exome AF: 0.723

Gnomad4 ASJ exome AF: 0.655

Gnomad4 EAS exome AF: 0.579

Gnomad4 SAS exome AF: 0.760

Gnomad4 FIN exome AF: 0.676

Gnomad4 NFE exome AF: 0.615

Gnomad4 OTH exome AF: 0.631

GnomAD4 genome AF: 0.620 AC: 94148 AN: 151898 Hom.: 29461 Cov.: 31 AF XY: 0.626 AC XY: 46443 AN XY: 74218

Gnomad4 AFR AF: 0.541

Gnomad4 AMR AF: 0.685

Gnomad4 ASJ AF: 0.655

Gnomad4 EAS AF: 0.651

Gnomad4 SAS AF: 0.776

Gnomad4 FIN AF: 0.688

Gnomad4 NFE AF: 0.625

Gnomad4 OTH AF: 0.637

Alfa AF: 0.631 Hom.: 21393

Bravo AF: 0.616

Asia WGS AF: 0.724 AC: 2520 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	0.34
Dann	Benign	0.60

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

Other links and lift over

dbSNP: rs11942576; hg19: chr4-109762918; COSMIC: COSV67645829;