10-97923224-T-C

Variant names:

• chr10-97923224-T-C
• rs894375
• NM_018058.7:c.558+40A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 8 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.901 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018058.7. 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
	CRTAC1	NM_018058.7	MANE Select	c.558+40A>G		intron	N/A	NP_060528.3
	CRTAC1	NM_001206528.3		c.558+40A>G		intron	N/A	NP_001193457.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CRTAC1	ENST00000370597.8	TSL:1 MANE Select	c.558+40A>G		intron	N/A	ENSP00000359629.3
	CRTAC1	ENST00000309155.3	TSL:1	c.534+40A>G		intron	N/A	ENSP00000310810.3
	CRTAC1	ENST00000370591.6	TSL:5	c.558+40A>G		intron	N/A	ENSP00000359623.2

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

GnomAD2 exomes AF: 0.805 AC: 198925 AN: 247068 AF XY: 0.797

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 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

African (AFR) AF: 0.744 AC: 24910 AN: 33462

American (AMR) AF: 0.889 AC: 39730 AN: 44670

Ashkenazi Jewish (ASJ) AF: 0.753 AC: 19651 AN: 26090

East Asian (EAS) AF: 0.921 AC: 36530 AN: 39664

South Asian (SAS) AF: 0.730 AC: 62935 AN: 86176

European-Finnish (FIN) AF: 0.779 AC: 40840 AN: 52450

Middle Eastern (MID) AF: 0.758 AC: 4369 AN: 5764

European-Non Finnish (NFE) AF: 0.801 AC: 889140 AN: 1110724

Other (OTH) AF: 0.797 AC: 48066 AN: 60300

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

African (AFR) AF: 0.749 AC: 31087 AN: 41498

American (AMR) AF: 0.841 AC: 12868 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.755 AC: 2622 AN: 3472

East Asian (EAS) AF: 0.923 AC: 4779 AN: 5180

South Asian (SAS) AF: 0.723 AC: 3485 AN: 4820

European-Finnish (FIN) AF: 0.780 AC: 8266 AN: 10598

Middle Eastern (MID) AF: 0.776 AC: 228 AN: 294

European-Non Finnish (NFE) AF: 0.797 AC: 54188 AN: 68006

Other (OTH) AF: 0.798 AC: 1683 AN: 2108

Alfa AF: 0.785 Hom.: 16659

Bravo AF: 0.797

Asia WGS AF: 0.804 AC: 2794 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.7
DANN	Benign	0.45
PhyloP100		-0.84
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: rs894375; hg19: chr10-99682981;