rs531676

Positions:

• chr10-97877821-G-A

Variant summary

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

The NM_018058.7(CRTAC1):​c.1819+2428C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.458 in 152,064 control chromosomes in the GnomAD database, including 16,299 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 0.46 (16299 hom., cov: 32)
• Consequence: CRTAC1 NM_018058.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.270

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=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.633 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CRTAC1	NM_018058.7	c.1819+2428C>T		intron_variant		ENST00000370597.8	NP_060528.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CRTAC1	ENST00000370597.8	c.1819+2428C>T		intron_variant		1	NM_018058.7	ENSP00000359629
CRTAC1	ENST00000413387.5	c.1464+2428C>T		intron_variant		2		ENSP00000408445

Frequencies

GnomAD3 genomes AF: 0.458 AC: 69591 AN: 151946 Hom.: 16297 Cov.: 32

Gnomad AFR AF: 0.382

Gnomad AMI AF: 0.430

Gnomad AMR AF: 0.498

Gnomad ASJ AF: 0.543

Gnomad EAS AF: 0.650

Gnomad SAS AF: 0.543

Gnomad FIN AF: 0.445

Gnomad MID AF: 0.468

Gnomad NFE AF: 0.473

Gnomad OTH AF: 0.460

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

GnomAD4 genome AF: 0.458 AC: 69619 AN: 152064 Hom.: 16299 Cov.: 32 AF XY: 0.459 AC XY: 34099 AN XY: 74330

Gnomad4 AFR AF: 0.382

Gnomad4 AMR AF: 0.498

Gnomad4 ASJ AF: 0.543

Gnomad4 EAS AF: 0.651

Gnomad4 SAS AF: 0.541

Gnomad4 FIN AF: 0.445

Gnomad4 NFE AF: 0.473

Gnomad4 OTH AF: 0.456

Alfa AF: 0.476 Hom.: 38097

Bravo AF: 0.458

Asia WGS AF: 0.559 AC: 1943 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.3
DANN	Benign	0.31

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: rs531676; hg19: chr10-99637578;