rs11189446

Variant names:

• chr10-97930107-C-T
• rs11189446
• NM_018058.7:c.421+6063G>A

Variant summary

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

The NM_018058.7(CRTAC1):​c.421+6063G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.813 in 152,158 control chromosomes in the GnomAD database, including 51,420 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 0.81 (51420 hom., cov: 33)
• Consequence: CRTAC1 NM_018058.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.642
• Publications: 1 publications found

Genes affected

CRTAC1 (HGNC:14882): (cartilage acidic protein 1) This gene encodes a glycosylated extracellular matrix protein that is found in the interterritorial matrix of articular deep zone cartilage. This protein is used as a marker to distinguish chondrocytes from osteoblasts and mesenchymal stem cells in culture. The presence of FG-GAP motifs and an RGD integrin-binding motif suggests that this protein may be involved in cell-cell or cell-matrix interactions. Copy number alterations in this gene have been observed in neurofibromatosis type 1-associated glomus tumors. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2011]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.882 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CRTAC1	NM_018058.7	c.421+6063G>A		intron_variant	Intron 3 of 14	ENST00000370597.8	NP_060528.3
CRTAC1	NM_001206528.3	c.421+6063G>A		intron_variant	Intron 3 of 14		NP_001193457.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CRTAC1	ENST00000370597.8	c.421+6063G>A		intron_variant	Intron 3 of 14	1	NM_018058.7	ENSP00000359629.3
CRTAC1	ENST00000309155.3	c.397+6063G>A		intron_variant	Intron 2 of 13	1		ENSP00000310810.3
CRTAC1	ENST00000370591.6	c.421+6063G>A		intron_variant	Intron 3 of 14	5		ENSP00000359623.2
CRTAC1	ENST00000413387.5	c.109+6063G>A		intron_variant	Intron 1 of 11	2		ENSP00000408445.1

Frequencies

GnomAD3 genomes AF: 0.813 AC: 123670 AN: 152040 Hom.: 51396 Cov.: 33

Gnomad AFR AF: 0.627

Gnomad AMI AF: 0.855

Gnomad AMR AF: 0.865

Gnomad ASJ AF: 0.875

Gnomad EAS AF: 0.857

Gnomad SAS AF: 0.860

Gnomad FIN AF: 0.923

Gnomad MID AF: 0.804

Gnomad NFE AF: 0.888

Gnomad OTH AF: 0.824

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

GnomAD4 genome AF: 0.813 AC: 123746 AN: 152158 Hom.: 51420 Cov.: 33 AF XY: 0.818 AC XY: 60824 AN XY: 74402

African (AFR) AF: 0.627 AC: 25988 AN: 41478

American (AMR) AF: 0.865 AC: 13215 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.875 AC: 3035 AN: 3470

East Asian (EAS) AF: 0.857 AC: 4431 AN: 5172

South Asian (SAS) AF: 0.860 AC: 4147 AN: 4820

European-Finnish (FIN) AF: 0.923 AC: 9796 AN: 10618

Middle Eastern (MID) AF: 0.806 AC: 237 AN: 294

European-Non Finnish (NFE) AF: 0.888 AC: 60383 AN: 68004

Other (OTH) AF: 0.824 AC: 1736 AN: 2108

Alfa AF: 0.839 Hom.: 7041

Bravo AF: 0.801

Asia WGS AF: 0.820 AC: 2855 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.052
DANN	Benign	0.45
PhyloP100		-0.64
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: rs11189446; hg19: chr10-99689864;