chr2-46659003-G-A

Variant names:

• chr2-46659003-G-A
• rs4953404
• ENST00000718244.1:n.209+10917G>A

Variant summary

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

The ENST00000718244.1(CRIPT):​n.209+10917G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.693 in 151,972 control chromosomes in the GnomAD database, including 36,843 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 0.69 (36843 hom., cov: 30)
• Consequence: CRIPT ENST00000718244.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.164
• Publications: 7 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=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.804 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+10917G>A		intron	N/A	ENSP00000520689.1
	CRIPT	ENST00000718246.1		n.*315+8707G>A		intron	N/A	ENSP00000520691.1

Frequencies

GnomAD3 genomes AF: 0.693 AC: 105252 AN: 151854 Hom.: 36820 Cov.: 30

Gnomad AFR AF: 0.632

Gnomad AMI AF: 0.825

Gnomad AMR AF: 0.777

Gnomad ASJ AF: 0.739

Gnomad EAS AF: 0.825

Gnomad SAS AF: 0.675

Gnomad FIN AF: 0.572

Gnomad MID AF: 0.763

Gnomad NFE AF: 0.717

Gnomad OTH AF: 0.711

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

GnomAD4 genome AF: 0.693 AC: 105325 AN: 151972 Hom.: 36843 Cov.: 30 AF XY: 0.690 AC XY: 51264 AN XY: 74262

African (AFR) AF: 0.632 AC: 26192 AN: 41438

American (AMR) AF: 0.777 AC: 11881 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.739 AC: 2564 AN: 3470

East Asian (EAS) AF: 0.825 AC: 4252 AN: 5156

South Asian (SAS) AF: 0.673 AC: 3245 AN: 4820

European-Finnish (FIN) AF: 0.572 AC: 6035 AN: 10542

Middle Eastern (MID) AF: 0.776 AC: 228 AN: 294

European-Non Finnish (NFE) AF: 0.717 AC: 48681 AN: 67942

Other (OTH) AF: 0.710 AC: 1496 AN: 2108

Alfa AF: 0.710 Hom.: 11149

Bravo AF: 0.708

Asia WGS AF: 0.719 AC: 2501 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.2
DANN	Benign	0.75
PhyloP100		0.16

Splicing

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

Other links and lift over

dbSNP: rs4953404; hg19: chr2-46886142;