rs571556212

Variant names:

• chr1-85745485-C-T
• rs571556212
• NM_152890.7:c.4459G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_152890.7(COL24A1):​c.4459G>A​(p.Ala1487Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0000118 in 1,609,766 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000046 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0000082 (0 hom.)
• Consequence: COL24A1 NM_152890.7 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.86
• Publications: 1 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.09888989).

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.4459G>A	p.Ala1487Thr	missense	Exon 56 of 60	NP_690850.2	Q17RW2-1
	COL24A1	NM_001349955.1		c.2359G>A	p.Ala787Thr	missense	Exon 56 of 60	NP_001336884.1
	COL24A1	NR_146340.2		n.4608G>A		non_coding_transcript_exon	Exon 57 of 61

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL24A1	ENST00000370571.7	TSL:1 MANE Select	c.4459G>A	p.Ala1487Thr	missense	Exon 56 of 60	ENSP00000359603.2	Q17RW2-1
	COL24A1	ENST00000426639.5	TSL:5	n.*1846G>A		non_coding_transcript_exon	Exon 55 of 59	ENSP00000409515.1	F8WDM8
	COL24A1	ENST00000426639.5	TSL:5	n.*1846G>A		3_prime_UTR	Exon 55 of 59	ENSP00000409515.1	F8WDM8

Frequencies

GnomAD3 genomes AF: 0.0000460 AC: 7 AN: 152100 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000611 AC: 15 AN: 245302 AF XY: 0.0000825

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000848

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000823 AC: 12 AN: 1457548 Hom.: 0 Cov.: 29 AF XY: 0.0000110 AC XY: 8 AN XY: 725132

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 33242

American (AMR) AF: 0.00 AC: 0 AN: 44114

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26062

East Asian (EAS) AF: 0.000305 AC: 12 AN: 39326

South Asian (SAS) AF: 0.00 AC: 0 AN: 85536

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52954

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5752

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1110360

Other (OTH) AF: 0.00 AC: 0 AN: 60202

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.00437189), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.0000460 AC: 7 AN: 152218 Hom.: 0 Cov.: 31 AF XY: 0.0000672 AC XY: 5 AN XY: 74420

African (AFR) AF: 0.00 AC: 0 AN: 41552

American (AMR) AF: 0.00 AC: 0 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00135 AC: 7 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10598

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67982

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000416

ExAC AF: 0.0000497 AC: 6

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Uncertain	0.040
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.022	T
Eigen	Uncertain	0.56
Eigen_PC	Uncertain	0.62
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.69	T
M_CAP	Benign	0.032	D
MetaRNN	Benign	0.099	T
MetaSVM	Uncertain	0.57	D
MutationAssessor	Uncertain	2.0	M
PhyloP100		4.9
PrimateAI	Uncertain	0.60	T
PROVEAN	Uncertain	-2.6	D
REVEL	Uncertain	0.50
Sift	Uncertain	0.0050	D
Sift4G	Benign	0.20	T
Polyphen		0.88	P
Vest4		0.51
MutPred		0.35		Gain of glycosylation at A1487 (P = 0.0098)
MVP		0.61
MPC		0.19
ClinPred		0.29	T
GERP RS		5.9
Varity_R		0.27
gMVP		0.37
Mutation Taster		=59/41	polymorphism

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: rs571556212; hg19: chr1-86211168;