rs3754551

Variant names:

• chr2-46617518-C-G
• rs3754551
• NM_014171.6:c.16+220C>G

Your query was ambiguous. Multiple possible variants found:

• chr2-46617518-C-G
• chr2-46617518-C-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_014171.6(CRIPT):​c.16+220C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0434 in 152,214 control chromosomes in the GnomAD database, including 245 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.043 (245 hom., cov: 31)
• Consequence: CRIPT NM_014171.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.85
• Publications: 2 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 2-46617518-C-G is Benign according to our data. Variant chr2-46617518-C-G is described in ClinVar as [Benign]. Clinvar id is 1226796.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.177 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CRIPT	NM_014171.6	c.16+220C>G		intron_variant	Intron 1 of 4	ENST00000238892.4	NP_054890.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CRIPT	ENST00000238892.4	c.16+220C>G		intron_variant	Intron 1 of 4	1	NM_014171.6	ENSP00000238892.3

Frequencies

GnomAD3 genomes AF: 0.0435 AC: 6617 AN: 152096 Hom.: 246 Cov.: 31

Gnomad AFR AF: 0.00905

Gnomad AMI AF: 0.0691

Gnomad AMR AF: 0.0335

Gnomad ASJ AF: 0.0637

Gnomad EAS AF: 0.187

Gnomad SAS AF: 0.0661

Gnomad FIN AF: 0.0930

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.0450

Gnomad OTH AF: 0.0426

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

GnomAD4 genome AF: 0.0434 AC: 6611 AN: 152214 Hom.: 245 Cov.: 31 AF XY: 0.0472 AC XY: 3512 AN XY: 74418

African (AFR) AF: 0.00903 AC: 375 AN: 41550

American (AMR) AF: 0.0335 AC: 512 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0637 AC: 221 AN: 3470

East Asian (EAS) AF: 0.187 AC: 964 AN: 5158

South Asian (SAS) AF: 0.0663 AC: 319 AN: 4810

European-Finnish (FIN) AF: 0.0930 AC: 986 AN: 10602

Middle Eastern (MID) AF: 0.0714 AC: 21 AN: 294

European-Non Finnish (NFE) AF: 0.0450 AC: 3061 AN: 68020

Other (OTH) AF: 0.0421 AC: 89 AN: 2112

Alfa AF: 0.0175 Hom.: 9

Bravo AF: 0.0381

Asia WGS AF: 0.0860 AC: 299 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 18, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.64
DANN	Benign	0.44
PhyloP100		-1.9
PromoterAI		0.032	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3754551; hg19: chr2-46844657;