2-46617518-C-G

Position:

• chr2-46617518-C-G

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
CRIPT	NM_014171.6	c.16+220C>G		intron_variant		ENST00000238892.4	NP_054890.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CRIPT	ENST00000238892.4	c.16+220C>G		intron_variant		1	NM_014171.6	ENSP00000238892	P1
CRIPT	ENST00000486447.1	n.608+495C>G		intron_variant, non_coding_transcript_variant		5

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

Gnomad4 AFR AF: 0.00903

Gnomad4 AMR AF: 0.0335

Gnomad4 ASJ AF: 0.0637

Gnomad4 EAS AF: 0.187

Gnomad4 SAS AF: 0.0663

Gnomad4 FIN AF: 0.0930

Gnomad4 NFE AF: 0.0450

Gnomad4 OTH AF: 0.0421

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

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 18, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.64
DANN	Benign	0.44

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

LitVar

Other links and lift over

dbSNP: rs3754551; hg19: chr2-46844657;