rs6735530

Positions:

• chr2-46621307-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014171.6(CRIPT):​c.137+1626T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.256 in 152,118 control chromosomes in the GnomAD database, including 8,323 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.26 (8323 hom., cov: 31)
• Consequence: CRIPT NM_014171.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.302

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.584 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CRIPT	NM_014171.6	c.137+1626T>C		intron_variant		ENST00000238892.4	NP_054890.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CRIPT	ENST00000238892.4	c.137+1626T>C		intron_variant		1	NM_014171.6	ENSP00000238892	P1
CRIPT	ENST00000486447.1	n.729+1626T>C		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.255 AC: 38803 AN: 152000 Hom.: 8298 Cov.: 31

Gnomad AFR AF: 0.590

Gnomad AMI AF: 0.0691

Gnomad AMR AF: 0.165

Gnomad ASJ AF: 0.183

Gnomad EAS AF: 0.0572

Gnomad SAS AF: 0.238

Gnomad FIN AF: 0.0834

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.123

Gnomad OTH AF: 0.211

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

GnomAD4 genome AF: 0.256 AC: 38877 AN: 152118 Hom.: 8323 Cov.: 31 AF XY: 0.250 AC XY: 18570 AN XY: 74388

Gnomad4 AFR AF: 0.590

Gnomad4 AMR AF: 0.165

Gnomad4 ASJ AF: 0.183

Gnomad4 EAS AF: 0.0571

Gnomad4 SAS AF: 0.237

Gnomad4 FIN AF: 0.0834

Gnomad4 NFE AF: 0.123

Gnomad4 OTH AF: 0.210

Alfa AF: 0.153 Hom.: 3683

Bravo AF: 0.275

Asia WGS AF: 0.179 AC: 624 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.7
DANN	Benign	0.33

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: rs6735530; hg19: chr2-46848446;