rs2297936

Variant names:

• chr10-97882531-C-T
• rs2297936
• NM_018058.7:c.1675+255G>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.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
• Publications: 5 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=-0.82).
• 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 rank	MANE	Protein	UniProt
CRTAC1	NM_018058.7	c.1675+255G>A		intron_variant	Intron 13 of 14	ENST00000370597.8	NP_060528.3
CRTAC1	NM_001206528.3	c.1675+255G>A		intron_variant	Intron 13 of 14		NP_001193457.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CRTAC1	ENST00000370597.8	c.1675+255G>A		intron_variant	Intron 13 of 14	1	NM_018058.7	ENSP00000359629.3

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

African (AFR) AF: 0.297 AC: 12316 AN: 41520

American (AMR) AF: 0.317 AC: 4856 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.252 AC: 875 AN: 3468

East Asian (EAS) AF: 0.273 AC: 1410 AN: 5174

South Asian (SAS) AF: 0.256 AC: 1231 AN: 4816

European-Finnish (FIN) AF: 0.338 AC: 3586 AN: 10602

Middle Eastern (MID) AF: 0.245 AC: 72 AN: 294

European-Non Finnish (NFE) AF: 0.316 AC: 21486 AN: 68008

Other (OTH) AF: 0.293 AC: 620 AN: 2114

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
PhyloP100		0.38
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: rs2297936; hg19: chr10-99642288; COSMIC: COSV53999922;