2-46651212-C-G

Variant names:

• chr2-46651212-C-G
• rs13406427
• XR_940058.3:n.3234C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The XR_940058.3(LOC105374584):​n.3234C>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.309 in 152,134 control chromosomes in the GnomAD database, including 7,806 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 (7806 hom., cov: 33)
• Consequence: LOC105374584 XR_940058.3 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0350
• Publications: 5 publications found

Genes affected

LOC105374584 (HGNC:):

CRIPT (HGNC:14312): (CXXC repeat containing interactor of PDZ3 domain) This gene encodes a protein that binds to the PDZ3 peptide recognition domain. The encoded protein may modulates protein interactions with the cytoskeleton. A mutation in this gene resulted in short stature with microcephaly and distinctive facies. [provided by RefSeq, Jun 2014]

CRIPT Gene-Disease associations (from GenCC):

• Rothmund-Thomson syndrome, type 3

  Inheritance: AR Classification: STRONG, MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.418 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000718244.1. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CRIPT	ENST00000718244.1		n.209+3126C>G		intron	N/A	ENSP00000520689.1
	CRIPT	ENST00000718246.1		n.*315+916C>G		intron	N/A	ENSP00000520691.1

Frequencies

GnomAD3 genomes AF: 0.309 AC: 47033 AN: 152016 Hom.: 7798 Cov.: 33

Gnomad AFR AF: 0.423

Gnomad AMI AF: 0.387

Gnomad AMR AF: 0.323

Gnomad ASJ AF: 0.309

Gnomad EAS AF: 0.0975

Gnomad SAS AF: 0.281

Gnomad FIN AF: 0.237

Gnomad MID AF: 0.301

Gnomad NFE AF: 0.266

Gnomad OTH AF: 0.289

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

GnomAD4 genome AF: 0.309 AC: 47073 AN: 152134 Hom.: 7806 Cov.: 33 AF XY: 0.309 AC XY: 23019 AN XY: 74380

African (AFR) AF: 0.423 AC: 17552 AN: 41496

American (AMR) AF: 0.324 AC: 4945 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.309 AC: 1071 AN: 3470

East Asian (EAS) AF: 0.0971 AC: 503 AN: 5180

South Asian (SAS) AF: 0.280 AC: 1351 AN: 4822

European-Finnish (FIN) AF: 0.237 AC: 2511 AN: 10578

Middle Eastern (MID) AF: 0.303 AC: 89 AN: 294

European-Non Finnish (NFE) AF: 0.266 AC: 18094 AN: 67988

Other (OTH) AF: 0.286 AC: 604 AN: 2110

Alfa AF: 0.137 Hom.: 212

Bravo AF: 0.319

Asia WGS AF: 0.219 AC: 761 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	5.0
DANN	Benign	0.64
PhyloP100		-0.035

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs13406427; hg19: chr2-46878351;