NM_018058.7:c.1311C>A

Variant names:

• chr10-97895891-G-T
• rs577537
• NM_018058.7:c.1311C>A

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_018058.7(CRTAC1):​c.1311C>A​(p.Gly437Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0577 in 1,611,826 control chromosomes in the GnomAD database, including 2,959 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. Synonymous variant affecting the same amino acid position (i.e. G437G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.056 (270 hom., cov: 32)
  • Exomes 𝑓: 0.058 (2689 hom.)
• Consequence: CRTAC1 NM_018058.7 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0640
• Publications: 7 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.62).
• BP7: Synonymous conserved (PhyloP=-0.064 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.061 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CRTAC1	NM_018058.7	MANE Select	c.1311C>A	p.Gly437Gly	synonymous	Exon 10 of 15	NP_060528.3
	CRTAC1	NM_001206528.3		c.1311C>A	p.Gly437Gly	synonymous	Exon 10 of 15	NP_001193457.1	Q9NQ79-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CRTAC1	ENST00000370597.8	TSL:1 MANE Select	c.1311C>A	p.Gly437Gly	synonymous	Exon 10 of 15	ENSP00000359629.3	Q9NQ79-1
	CRTAC1	ENST00000309155.4	TSL:1	c.1287C>A	p.Gly429Gly	synonymous	Exon 10 of 15	ENSP00000310810.3
	CRTAC1	ENST00000856696.1		c.1356C>A	p.Gly452Gly	synonymous	Exon 11 of 16	ENSP00000526755.1

Frequencies

GnomAD3 genomes AF: 0.0558 AC: 8494 AN: 152124 Hom.: 272 Cov.: 32

Gnomad AFR AF: 0.0516

Gnomad AMI AF: 0.0681

Gnomad AMR AF: 0.0624

Gnomad ASJ AF: 0.0476

Gnomad EAS AF: 0.000963

Gnomad SAS AF: 0.0299

Gnomad FIN AF: 0.0565

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.0626

Gnomad OTH AF: 0.0646

GnomAD2 exomes AF: 0.0502 AC: 12592 AN: 250706 AF XY: 0.0509

Gnomad AFR exome AF: 0.0504

Gnomad AMR exome AF: 0.0405

Gnomad ASJ exome AF: 0.0478

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.0632

Gnomad NFE exome AF: 0.0640

Gnomad OTH exome AF: 0.0561

GnomAD4 exome AF: 0.0579 AC: 84451 AN: 1459584 Hom.: 2689 Cov.: 31 AF XY: 0.0576 AC XY: 41832 AN XY: 725822

African (AFR) AF: 0.0527 AC: 1764 AN: 33446

American (AMR) AF: 0.0431 AC: 1928 AN: 44686

Ashkenazi Jewish (ASJ) AF: 0.0502 AC: 1310 AN: 26118

East Asian (EAS) AF: 0.000227 AC: 9 AN: 39658

South Asian (SAS) AF: 0.0317 AC: 2737 AN: 86214

European-Finnish (FIN) AF: 0.0597 AC: 3182 AN: 53322

Middle Eastern (MID) AF: 0.0874 AC: 503 AN: 5756

European-Non Finnish (NFE) AF: 0.0628 AC: 69757 AN: 1110094

Other (OTH) AF: 0.0541 AC: 3261 AN: 60290

GnomAD4 genome AF: 0.0558 AC: 8488 AN: 152242 Hom.: 270 Cov.: 32 AF XY: 0.0553 AC XY: 4115 AN XY: 74446

African (AFR) AF: 0.0515 AC: 2137 AN: 41532

American (AMR) AF: 0.0624 AC: 954 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0476 AC: 165 AN: 3468

East Asian (EAS) AF: 0.000966 AC: 5 AN: 5178

South Asian (SAS) AF: 0.0295 AC: 142 AN: 4820

European-Finnish (FIN) AF: 0.0565 AC: 600 AN: 10614

Middle Eastern (MID) AF: 0.0952 AC: 28 AN: 294

European-Non Finnish (NFE) AF: 0.0626 AC: 4259 AN: 68014

Other (OTH) AF: 0.0644 AC: 136 AN: 2112

Alfa AF: 0.0601 Hom.: 502

Bravo AF: 0.0560

Asia WGS AF: 0.0120 AC: 41 AN: 3478

EpiCase AF: 0.0680

EpiControl AF: 0.0660

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	1.0
DANN	Benign	0.77
PhyloP100		-0.064
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: rs577537; hg19: chr10-99655648; COSMIC: COSV108150109;