rs1963939

chr4-108818311-A-Gchr4-108818311-A-T

Variant summary

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

The NM_198721.4(COL25A1):c.1924-876T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.491 in 151,558 control chromosomes in the GnomAD database, including 19,165 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 0.49 (19165 hom., cov: 33)
• Consequence: COL25A1 NM_198721.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0160

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.58).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.571 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL25A1	NM_198721.4	c.1924-876T>C		intron_variant		ENST00000399132.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL25A1	ENST00000399132.6	c.1924-876T>C		intron_variant		5	NM_198721.4
COL25A1	ENST00000512961.5	c.47-876T>C		intron_variant		5
COL25A1	ENST00000642955.1	c.2050-876T>C		intron_variant				P1
COL25A1	ENST00000494183.5	c.*218-876T>C		intron_variant, NMD_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.492 AC: 74474 AN: 151438 Hom.: 19158 Cov.: 33

Gnomad AFR AF: 0.314

Gnomad AMI AF: 0.560

Gnomad AMR AF: 0.511

Gnomad ASJ AF: 0.588

Gnomad EAS AF: 0.523

Gnomad SAS AF: 0.588

Gnomad FIN AF: 0.568

Gnomad MID AF: 0.642

Gnomad NFE AF: 0.568

Gnomad OTH AF: 0.509

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

GnomAD4 genome AF: 0.491 AC: 74490 AN: 151558 Hom.: 19165 Cov.: 33 AF XY: 0.494 AC XY: 36541 AN XY: 74036

Gnomad4 AFR AF: 0.314

Gnomad4 AMR AF: 0.511

Gnomad4 ASJ AF: 0.588

Gnomad4 EAS AF: 0.523

Gnomad4 SAS AF: 0.589

Gnomad4 FIN AF: 0.568

Gnomad4 NFE AF: 0.568

Gnomad4 OTH AF: 0.504

Alfa AF: 0.520 Hom.: 2612

Bravo AF: 0.481

Asia WGS AF: 0.562 AC: 1937 AN: 3448

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
Cadd	Benign	1.5
Dann	Benign	0.86

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: rs1963939; hg19: chr4-109739467;