4-109039086-A-G

Position:

• chr4-109039086-A-G

Variant summary

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

The NM_198721.4(COL25A1):​c.420+9082T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.511 in 151,518 control chromosomes in the GnomAD database, including 21,894 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 0.51 (21894 hom., cov: 30)
• Consequence: COL25A1 NM_198721.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.734

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]

LOC124900756 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.739 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COL25A1	NM_198721.4	c.420+9082T>C		intron_variant		ENST00000399132.6	NP_942014.1
LOC124900756	XR_007058225.1	n.462-573A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COL25A1	ENST00000399132.6	c.420+9082T>C		intron_variant		5	NM_198721.4	ENSP00000382083

Frequencies

GnomAD3 genomes AF: 0.511 AC: 77343 AN: 151402 Hom.: 21846 Cov.: 30

Gnomad AFR AF: 0.746

Gnomad AMI AF: 0.445

Gnomad AMR AF: 0.569

Gnomad ASJ AF: 0.456

Gnomad EAS AF: 0.665

Gnomad SAS AF: 0.475

Gnomad FIN AF: 0.338

Gnomad MID AF: 0.544

Gnomad NFE AF: 0.376

Gnomad OTH AF: 0.505

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

GnomAD4 genome AF: 0.511 AC: 77462 AN: 151518 Hom.: 21894 Cov.: 30 AF XY: 0.513 AC XY: 37989 AN XY: 74016

Gnomad4 AFR AF: 0.746

Gnomad4 AMR AF: 0.570

Gnomad4 ASJ AF: 0.456

Gnomad4 EAS AF: 0.666

Gnomad4 SAS AF: 0.476

Gnomad4 FIN AF: 0.338

Gnomad4 NFE AF: 0.376

Gnomad4 OTH AF: 0.510

Alfa AF: 0.451 Hom.: 2806

Bravo AF: 0.539

Asia WGS AF: 0.584 AC: 2028 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.32
DANN	Benign	0.37

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: rs794149; hg19: chr4-109960242;