chr2-46617108-G-T

Position:

• chr2-46617108-G-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000486447.1(CRIPT):​n.608+85G>T variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.111 in 843,824 control chromosomes in the GnomAD database, including 7,845 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.16 (3290 hom., cov: 32)
  • Exomes 𝑓: 0.099 (4555 hom.)
• Consequence: CRIPT ENST00000486447.1 intron, non_coding_transcript
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0690

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=-0.79).
• BP6: Variant 2-46617108-G-T is Benign according to our data. Variant chr2-46617108-G-T is described in ClinVar as [Benign]. Clinvar id is 1251822.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.36 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CRIPT	ENST00000486447.1	n.608+85G>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.163 AC: 24805 AN: 152086 Hom.: 3279 Cov.: 32

Gnomad AFR AF: 0.365

Gnomad AMI AF: 0.0504

Gnomad AMR AF: 0.112

Gnomad ASJ AF: 0.101

Gnomad EAS AF: 0.0392

Gnomad SAS AF: 0.150

Gnomad FIN AF: 0.0468

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.0858

Gnomad OTH AF: 0.133

GnomAD4 exome AF: 0.0992 AC: 68623 AN: 691620 Hom.: 4555 Cov.: 9 AF XY: 0.0998 AC XY: 36189 AN XY: 362546

Gnomad4 AFR exome AF: 0.374

Gnomad4 AMR exome AF: 0.0997

Gnomad4 ASJ exome AF: 0.104

Gnomad4 EAS exome AF: 0.0467

Gnomad4 SAS exome AF: 0.144

Gnomad4 FIN exome AF: 0.0553

Gnomad4 NFE exome AF: 0.0880

Gnomad4 OTH exome AF: 0.106

GnomAD4 genome AF: 0.163 AC: 24849 AN: 152204 Hom.: 3290 Cov.: 32 AF XY: 0.158 AC XY: 11725 AN XY: 74432

Gnomad4 AFR AF: 0.365

Gnomad4 AMR AF: 0.112

Gnomad4 ASJ AF: 0.101

Gnomad4 EAS AF: 0.0393

Gnomad4 SAS AF: 0.149

Gnomad4 FIN AF: 0.0468

Gnomad4 NFE AF: 0.0858

Gnomad4 OTH AF: 0.133

Alfa AF: 0.0891 Hom.: 225

Bravo AF: 0.177

Asia WGS AF: 0.111 AC: 388 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	clinical testing	GeneDx	Nov 10, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	7.8
DANN	Benign	0.91

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: rs113423551; hg19: chr2-46844247;