rs6735530

Variant names:

• chr2-46621307-T-C
• rs6735530
• NM_014171.6:c.137+1626T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 8 publications found

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: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014171.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CRIPT	NM_014171.6	MANE Select	c.137+1626T>C		intron	N/A	NP_054890.1	Q9P021

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CRIPT	ENST00000238892.4	TSL:1 MANE Select	c.137+1626T>C		intron	N/A	ENSP00000238892.3	Q9P021
	CRIPT	ENST00000923190.1		c.137+1626T>C		intron	N/A	ENSP00000593249.1
	CRIPT	ENST00000486447.1	TSL:5	n.729+1626T>C		intron	N/A

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

African (AFR) AF: 0.590 AC: 24463 AN: 41440

American (AMR) AF: 0.165 AC: 2519 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.183 AC: 634 AN: 3470

East Asian (EAS) AF: 0.0571 AC: 296 AN: 5184

South Asian (SAS) AF: 0.237 AC: 1141 AN: 4822

European-Finnish (FIN) AF: 0.0834 AC: 884 AN: 10602

Middle Eastern (MID) AF: 0.190 AC: 56 AN: 294

European-Non Finnish (NFE) AF: 0.123 AC: 8378 AN: 67990

Other (OTH) AF: 0.210 AC: 443 AN: 2112

Alfa AF: 0.167 Hom.: 5752

Bravo AF: 0.275

Asia WGS AF: 0.179 AC: 624 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.7
DANN	Benign	0.33
PhyloP100		-0.30
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6735530; hg19: chr2-46848446;