1-85905466-T-C

Variant names:

• chr1-85905466-T-C
• rs1858556
• NM_152890.7:c.2778+1728A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_152890.7(COL24A1):​c.2778+1728A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.313 in 151,910 control chromosomes in the GnomAD database, including 8,464 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 0.31 (8464 hom., cov: 31)
• Consequence: COL24A1 NM_152890.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.37
• Publications: 3 publications found

Genes affected

COL24A1 (HGNC:20821): (collagen type XXIV alpha 1 chain) This gene is a member of the collagen gene family and is thought to regulate type I collagen fibrillogenesis during fetal development. [provided by RefSeq, Mar 2017]

COL24A1 Gene-Disease associations (from GenCC):

• Tourette syndrome

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.493 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152890.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL24A1	NM_152890.7	MANE Select	c.2778+1728A>G		intron	N/A	NP_690850.2	Q17RW2-1
	COL24A1	NM_001349955.1		c.678+1728A>G		intron	N/A	NP_001336884.1
	COL24A1	NR_146340.2		n.2971+1728A>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL24A1	ENST00000370571.7	TSL:1 MANE Select	c.2778+1728A>G		intron	N/A	ENSP00000359603.2	Q17RW2-1
	COL24A1	ENST00000426639.5	TSL:5	n.*228+1728A>G		intron	N/A	ENSP00000409515.1	F8WDM8

Frequencies

GnomAD3 genomes AF: 0.313 AC: 47578 AN: 151790 Hom.: 8457 Cov.: 31

Gnomad AFR AF: 0.160

Gnomad AMI AF: 0.250

Gnomad AMR AF: 0.436

Gnomad ASJ AF: 0.312

Gnomad EAS AF: 0.509

Gnomad SAS AF: 0.326

Gnomad FIN AF: 0.449

Gnomad MID AF: 0.342

Gnomad NFE AF: 0.343

Gnomad OTH AF: 0.325

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

GnomAD4 genome AF: 0.313 AC: 47596 AN: 151910 Hom.: 8464 Cov.: 31 AF XY: 0.322 AC XY: 23919 AN XY: 74250

African (AFR) AF: 0.160 AC: 6621 AN: 41470

American (AMR) AF: 0.436 AC: 6649 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.312 AC: 1081 AN: 3468

East Asian (EAS) AF: 0.509 AC: 2630 AN: 5164

South Asian (SAS) AF: 0.327 AC: 1572 AN: 4814

European-Finnish (FIN) AF: 0.449 AC: 4732 AN: 10546

Middle Eastern (MID) AF: 0.344 AC: 101 AN: 294

European-Non Finnish (NFE) AF: 0.343 AC: 23306 AN: 67898

Other (OTH) AF: 0.321 AC: 676 AN: 2106

Alfa AF: 0.331 Hom.: 1582

Bravo AF: 0.308

Asia WGS AF: 0.398 AC: 1380 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	7.9
DANN	Benign	0.68
PhyloP100		2.4
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1858556; hg19: chr1-86371149;