2-46618710-A-G

Position:

• chr2-46618710-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_014171.6(CRIPT):​c.17-63A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.299 in 1,047,444 control chromosomes in the GnomAD database, including 49,052 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.28 (6304 hom., cov: 32)
  • Exomes 𝑓: 0.30 (42748 hom.)
• Consequence: CRIPT NM_014171.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.08

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BP6: Variant 2-46618710-A-G is Benign according to our data. Variant chr2-46618710-A-G is described in ClinVar as [Benign]. Clinvar id is 1259318.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.336 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CRIPT	NM_014171.6	c.17-63A>G		intron_variant		ENST00000238892.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CRIPT	ENST00000238892.4	c.17-63A>G		intron_variant		1	NM_014171.6	P1
CRIPT	ENST00000486447.1	n.609-63A>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.279 AC: 42327 AN: 151954 Hom.: 6303 Cov.: 32

Gnomad AFR AF: 0.193

Gnomad AMI AF: 0.440

Gnomad AMR AF: 0.343

Gnomad ASJ AF: 0.385

Gnomad EAS AF: 0.105

Gnomad SAS AF: 0.255

Gnomad FIN AF: 0.273

Gnomad MID AF: 0.283

Gnomad NFE AF: 0.324

Gnomad OTH AF: 0.282

GnomAD4 exome AF: 0.302 AC: 270622 AN: 895372 Hom.: 42748 AF XY: 0.302 AC XY: 140953 AN XY: 466422

Gnomad4 AFR exome AF: 0.184

Gnomad4 AMR exome AF: 0.369

Gnomad4 ASJ exome AF: 0.390

Gnomad4 EAS exome AF: 0.0821

Gnomad4 SAS exome AF: 0.266

Gnomad4 FIN exome AF: 0.288

Gnomad4 NFE exome AF: 0.317

Gnomad4 OTH exome AF: 0.302

GnomAD4 genome AF: 0.278 AC: 42348 AN: 152072 Hom.: 6304 Cov.: 32 AF XY: 0.277 AC XY: 20567 AN XY: 74308

Gnomad4 AFR AF: 0.193

Gnomad4 AMR AF: 0.344

Gnomad4 ASJ AF: 0.385

Gnomad4 EAS AF: 0.105

Gnomad4 SAS AF: 0.256

Gnomad4 FIN AF: 0.273

Gnomad4 NFE AF: 0.324

Gnomad4 OTH AF: 0.278

Alfa AF: 0.314 Hom.: 15641

Bravo AF: 0.275

Asia WGS AF: 0.197 AC: 687 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

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	-0.73
CADD	Benign	7.8
DANN	Benign	0.73

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: rs2122715; hg19: chr2-46845849;