chr2-46680488-C-G

Variant names:

• chr2-46680488-C-G
• rs1456017
• ENST00000718244.1:n.*62-569C>G

Variant summary

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

The ENST00000718244.1(CRIPT):​n.*62-569C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.521 in 151,828 control chromosomes in the GnomAD database, including 21,111 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 0.52 (21111 hom., cov: 31)
• Consequence: CRIPT ENST00000718244.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.119
• Publications: 4 publications found

Genes affected

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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.627 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

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CRIPT	ENST00000718244.1		n.*62-569C>G		intron	N/A	ENSP00000520689.1
	CRIPT	ENST00000718246.1		n.*414-569C>G		intron	N/A	ENSP00000520691.1

Frequencies

GnomAD3 genomes AF: 0.521 AC: 79053 AN: 151710 Hom.: 21107 Cov.: 31

Gnomad AFR AF: 0.422

Gnomad AMI AF: 0.709

Gnomad AMR AF: 0.637

Gnomad ASJ AF: 0.669

Gnomad EAS AF: 0.645

Gnomad SAS AF: 0.600

Gnomad FIN AF: 0.451

Gnomad MID AF: 0.687

Gnomad NFE AF: 0.539

Gnomad OTH AF: 0.567

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

GnomAD4 genome AF: 0.521 AC: 79081 AN: 151828 Hom.: 21111 Cov.: 31 AF XY: 0.524 AC XY: 38886 AN XY: 74210

African (AFR) AF: 0.422 AC: 17436 AN: 41350

American (AMR) AF: 0.637 AC: 9720 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.669 AC: 2319 AN: 3468

East Asian (EAS) AF: 0.645 AC: 3333 AN: 5168

South Asian (SAS) AF: 0.598 AC: 2882 AN: 4820

European-Finnish (FIN) AF: 0.451 AC: 4740 AN: 10508

Middle Eastern (MID) AF: 0.701 AC: 206 AN: 294

European-Non Finnish (NFE) AF: 0.539 AC: 36610 AN: 67948

Other (OTH) AF: 0.565 AC: 1190 AN: 2108

Alfa AF: 0.503 Hom.: 2418

Bravo AF: 0.533

Asia WGS AF: 0.620 AC: 2154 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.2
DANN	Benign	0.66
PhyloP100		0.12

Splicing

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

Other links and lift over

dbSNP: rs1456017; hg19: chr2-46907627;