1-85911345-C-T

Variant names:

• chr1-85911345-C-T
• rs10493777
• NM_152890.7:c.2616+35G>A

Variant summary

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

The NM_152890.7(COL24A1):​c.2616+35G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.347 in 1,552,428 control chromosomes in the GnomAD database, including 97,516 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 (8479 hom., cov: 31)
  • Exomes 𝑓: 0.35 (89037 hom.)
• Consequence: COL24A1 NM_152890.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0220
• Publications: 5 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=-0.84).
• 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL24A1	NM_152890.7	MANE Select	c.2616+35G>A		intron	N/A	NP_690850.2
	COL24A1	NM_001349955.1		c.516+35G>A		intron	N/A	NP_001336884.1
	COL24A1	NR_146340.2		n.2809+35G>A		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL24A1	ENST00000370571.7	TSL:1 MANE Select	c.2616+35G>A		intron	N/A	ENSP00000359603.2
	COL24A1	ENST00000426639.5	TSL:5	n.*66+35G>A		intron	N/A	ENSP00000409515.1

Frequencies

GnomAD3 genomes AF: 0.314 AC: 47587 AN: 151752 Hom.: 8472 Cov.: 31

Gnomad AFR AF: 0.160

Gnomad AMI AF: 0.250

Gnomad AMR AF: 0.436

Gnomad ASJ AF: 0.311

Gnomad EAS AF: 0.509

Gnomad SAS AF: 0.327

Gnomad FIN AF: 0.450

Gnomad MID AF: 0.344

Gnomad NFE AF: 0.343

Gnomad OTH AF: 0.327

GnomAD2 exomes AF: 0.373 AC: 88913 AN: 238184 AF XY: 0.368

Gnomad AFR exome AF: 0.152

Gnomad AMR exome AF: 0.531

Gnomad ASJ exome AF: 0.310

Gnomad EAS exome AF: 0.525

Gnomad FIN exome AF: 0.464

Gnomad NFE exome AF: 0.341

Gnomad OTH exome AF: 0.353

GnomAD4 exome AF: 0.351 AC: 491563 AN: 1400556 Hom.: 89037 Cov.: 23 AF XY: 0.349 AC XY: 244509 AN XY: 700202

African (AFR) AF: 0.158 AC: 4970 AN: 31468

American (AMR) AF: 0.519 AC: 21088 AN: 40638

Ashkenazi Jewish (ASJ) AF: 0.315 AC: 8007 AN: 25420

East Asian (EAS) AF: 0.504 AC: 19818 AN: 39356

South Asian (SAS) AF: 0.315 AC: 26137 AN: 82956

European-Finnish (FIN) AF: 0.457 AC: 24282 AN: 53140

Middle Eastern (MID) AF: 0.351 AC: 1981 AN: 5636

European-Non Finnish (NFE) AF: 0.343 AC: 365344 AN: 1063736

Other (OTH) AF: 0.343 AC: 19936 AN: 58206

GnomAD4 genome AF: 0.313 AC: 47605 AN: 151872 Hom.: 8479 Cov.: 31 AF XY: 0.322 AC XY: 23922 AN XY: 74214

African (AFR) AF: 0.160 AC: 6626 AN: 41486

American (AMR) AF: 0.437 AC: 6657 AN: 15230

Ashkenazi Jewish (ASJ) AF: 0.311 AC: 1081 AN: 3472

East Asian (EAS) AF: 0.510 AC: 2629 AN: 5158

South Asian (SAS) AF: 0.328 AC: 1580 AN: 4820

European-Finnish (FIN) AF: 0.450 AC: 4733 AN: 10524

Middle Eastern (MID) AF: 0.346 AC: 101 AN: 292

European-Non Finnish (NFE) AF: 0.343 AC: 23290 AN: 67872

Other (OTH) AF: 0.323 AC: 680 AN: 2106

Alfa AF: 0.326 Hom.: 2476

Bravo AF: 0.308

Asia WGS AF: 0.396 AC: 1376 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.7
DANN	Benign	0.43
PhyloP100		0.022
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10493777; hg19: chr1-86377028; COSMIC: COSV65305391;