rs2297936

Positions:

• chr10-97882531-C-T

Variant summary

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

The NM_018058.7(CRTAC1):​c.1675+255G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.307 in 152,210 control chromosomes in the GnomAD database, including 7,211 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 0.31 (7211 hom., cov: 33)
• Consequence: CRTAC1 NM_018058.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.383

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=-0.82).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.312 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CRTAC1	NM_018058.7	c.1675+255G>A		intron_variant		ENST00000370597.8
CRTAC1	NM_001206528.3	c.1675+255G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CRTAC1	ENST00000370597.8	c.1675+255G>A		intron_variant		1	NM_018058.7

Frequencies

GnomAD3 genomes AF: 0.307 AC: 46658 AN: 152092 Hom.: 7203 Cov.: 33

Gnomad AFR AF: 0.297

Gnomad AMI AF: 0.270

Gnomad AMR AF: 0.317

Gnomad ASJ AF: 0.252

Gnomad EAS AF: 0.273

Gnomad SAS AF: 0.255

Gnomad FIN AF: 0.338

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.316

Gnomad OTH AF: 0.288

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

GnomAD4 genome AF: 0.307 AC: 46698 AN: 152210 Hom.: 7211 Cov.: 33 AF XY: 0.308 AC XY: 22925 AN XY: 74422

Gnomad4 AFR AF: 0.297

Gnomad4 AMR AF: 0.317

Gnomad4 ASJ AF: 0.252

Gnomad4 EAS AF: 0.273

Gnomad4 SAS AF: 0.256

Gnomad4 FIN AF: 0.338

Gnomad4 NFE AF: 0.316

Gnomad4 OTH AF: 0.293

Alfa AF: 0.311 Hom.: 1522

Bravo AF: 0.305

Asia WGS AF: 0.276 AC: 961 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	6.4
DANN	Benign	0.64

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: rs2297936; hg19: chr10-99642288; COSMIC: COSV53999922;