Genetic Variant NM_014171.6:c.16+220C>G (chr2-46617518-C-G) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.85

Publications

2 publications found

Variant links:

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

CRIPT links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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 link	c.16+220C>G		intron_variant	Intron 1 of 4	ENST00000238892.4	NP_054890.1	Q9P021

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CRIPT	ENST00000238892.4 link	c.16+220C>G		intron_variant	Intron 1 of 4	1	NM_014171.6	ENSP00000238892.3		Q9P021

Frequencies

GnomAD3 genomes

AF:

0.0435

AC:

6617

AN:

152096

Hom.:

246

Cov.:

show subpopulations

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.:

AF XY:

0.0472

AC XY:

3512

AN XY:

74418

show subpopulations

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:

AN:

294

European-Non Finnish (NFE)

AF:

0.0450

AC:

3061

AN:

68020

Other (OTH)

AF:

0.0421

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

309

617

926

1234

1543

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0175

Hom.:

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

LINK: link

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

(source)

DANN

Benign

0.44

PhyloP100

-1.9

PromoterAI

0.032

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Publications

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NM_014171.6:c.16+220C>G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over