10-97923224-T-C

Position:

• chr10-97923224-T-C

Variant summary

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

The NM_018058.7(CRTAC1):​c.558+40A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.798 in 1,611,490 control chromosomes in the GnomAD database, including 514,680 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 0.79 (47426 hom., cov: 34)
  • Exomes 𝑓: 0.80 (467254 hom.)
• Consequence: CRTAC1 NM_018058.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.841

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.901 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CRTAC1	NM_018058.7	c.558+40A>G		intron_variant		ENST00000370597.8
CRTAC1	NM_001206528.3	c.558+40A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CRTAC1	ENST00000370597.8	c.558+40A>G		intron_variant		1	NM_018058.7
CRTAC1	ENST00000309155.3	c.534+40A>G		intron_variant		1
CRTAC1	ENST00000370591.6	c.558+40A>G		intron_variant		5		P1
CRTAC1	ENST00000413387.5	c.246+40A>G		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.788 AC: 119865 AN: 152072 Hom.: 47384 Cov.: 34

Gnomad AFR AF: 0.749

Gnomad AMI AF: 0.828

Gnomad AMR AF: 0.841

Gnomad ASJ AF: 0.755

Gnomad EAS AF: 0.923

Gnomad SAS AF: 0.723

Gnomad FIN AF: 0.780

Gnomad MID AF: 0.769

Gnomad NFE AF: 0.797

Gnomad OTH AF: 0.802

GnomAD3 exomes AF: 0.805 AC: 198925 AN: 247068 Hom.: 80475 AF XY: 0.797 AC XY: 106824 AN XY: 133972

Gnomad AFR exome AF: 0.750

Gnomad AMR exome AF: 0.898

Gnomad ASJ exome AF: 0.755

Gnomad EAS exome AF: 0.921

Gnomad SAS exome AF: 0.729

Gnomad FIN exome AF: 0.775

Gnomad NFE exome AF: 0.797

Gnomad OTH exome AF: 0.794

GnomAD4 exome AF: 0.799 AC: 1166171 AN: 1459300 Hom.: 467254 Cov.: 37 AF XY: 0.796 AC XY: 577735 AN XY: 725842

Gnomad4 AFR exome AF: 0.744

Gnomad4 AMR exome AF: 0.889

Gnomad4 ASJ exome AF: 0.753

Gnomad4 EAS exome AF: 0.921

Gnomad4 SAS exome AF: 0.730

Gnomad4 FIN exome AF: 0.779

Gnomad4 NFE exome AF: 0.801

Gnomad4 OTH exome AF: 0.797

GnomAD4 genome AF: 0.788 AC: 119961 AN: 152190 Hom.: 47426 Cov.: 34 AF XY: 0.788 AC XY: 58626 AN XY: 74412

Gnomad4 AFR AF: 0.749

Gnomad4 AMR AF: 0.841

Gnomad4 ASJ AF: 0.755

Gnomad4 EAS AF: 0.923

Gnomad4 SAS AF: 0.723

Gnomad4 FIN AF: 0.780

Gnomad4 NFE AF: 0.797

Gnomad4 OTH AF: 0.798

Alfa AF: 0.782 Hom.: 9933

Bravo AF: 0.797

Asia WGS AF: 0.804 AC: 2794 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.7
DANN	Benign	0.45

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: rs894375; hg19: chr10-99682981;