rs2881504

Variant names:

• chr2-46651930-A-G
• rs2881504
• XR_940058.3:n.3952A>G

Your query was ambiguous. Multiple possible variants found:

• chr2-46651930-A-G
• chr2-46651930-A-T

Variant summary

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

The XR_940058.3(LOC105374584):​n.3952A>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 0.419 in 152,084 control chromosomes in the GnomAD database, including 14,716 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 0.42 (14716 hom., cov: 32)
• Consequence: LOC105374584 XR_940058.3 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0530
• Publications: 6 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.619 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC105374584	XR_940058.3	n.3952A>G		non_coding_transcript_exon_variant	Exon 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CRIPT	ENST00000718244.1	n.209+3844A>G		intron_variant	Intron 4 of 5			ENSP00000520689.1
CRIPT	ENST00000718246.1	n.*315+1634A>G		intron_variant	Intron 8 of 9			ENSP00000520691.1

Frequencies

GnomAD3 genomes AF: 0.419 AC: 63664 AN: 151966 Hom.: 14699 Cov.: 32

Gnomad AFR AF: 0.626

Gnomad AMI AF: 0.430

Gnomad AMR AF: 0.381

Gnomad ASJ AF: 0.338

Gnomad EAS AF: 0.110

Gnomad SAS AF: 0.344

Gnomad FIN AF: 0.305

Gnomad MID AF: 0.326

Gnomad NFE AF: 0.354

Gnomad OTH AF: 0.373

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

GnomAD4 genome AF: 0.419 AC: 63717 AN: 152084 Hom.: 14716 Cov.: 32 AF XY: 0.415 AC XY: 30856 AN XY: 74316

African (AFR) AF: 0.625 AC: 25957 AN: 41500

American (AMR) AF: 0.381 AC: 5821 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.338 AC: 1173 AN: 3470

East Asian (EAS) AF: 0.110 AC: 568 AN: 5174

South Asian (SAS) AF: 0.342 AC: 1652 AN: 4824

European-Finnish (FIN) AF: 0.305 AC: 3223 AN: 10566

Middle Eastern (MID) AF: 0.327 AC: 96 AN: 294

European-Non Finnish (NFE) AF: 0.354 AC: 24058 AN: 67968

Other (OTH) AF: 0.369 AC: 777 AN: 2106

Alfa AF: 0.360 Hom.: 25788

Bravo AF: 0.433

Asia WGS AF: 0.252 AC: 879 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.1
DANN	Benign	0.61
PhyloP100		-0.053

Splicing

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

Other links and lift over

dbSNP: rs2881504; hg19: chr2-46879069;