2-46681060-C-T

Variant names:

• chr2-46681060-C-T
• rs10495936
• ENST00000718244.1:n.*65C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000718246.1(CRIPT):​n.*417C>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.343 in 152,084 control chromosomes in the GnomAD database, including 9,054 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 0.34 (9054 hom., cov: 32)
• Consequence: CRIPT ENST00000718246.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.287
• Publications: 5 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: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.64).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.478 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000718246.1. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CRIPT	ENST00000718244.1		n.*65C>T		non_coding_transcript_exon	Exon 6 of 6	ENSP00000520689.1	A0ABB0MV94
	CRIPT	ENST00000718246.1		n.*417C>T		non_coding_transcript_exon	Exon 10 of 10	ENSP00000520691.1	Q9P021
	CRIPT	ENST00000718244.1		n.*65C>T		3_prime_UTR	Exon 6 of 6	ENSP00000520689.1	A0ABB0MV94

Frequencies

GnomAD3 genomes AF: 0.343 AC: 52108 AN: 151966 Hom.: 9045 Cov.: 32

Gnomad AFR AF: 0.323

Gnomad AMI AF: 0.319

Gnomad AMR AF: 0.360

Gnomad ASJ AF: 0.420

Gnomad EAS AF: 0.493

Gnomad SAS AF: 0.438

Gnomad FIN AF: 0.315

Gnomad MID AF: 0.487

Gnomad NFE AF: 0.332

Gnomad OTH AF: 0.376

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

GnomAD4 genome AF: 0.343 AC: 52136 AN: 152084 Hom.: 9054 Cov.: 32 AF XY: 0.347 AC XY: 25805 AN XY: 74332

African (AFR) AF: 0.323 AC: 13380 AN: 41478

American (AMR) AF: 0.361 AC: 5511 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.420 AC: 1459 AN: 3470

East Asian (EAS) AF: 0.494 AC: 2558 AN: 5176

South Asian (SAS) AF: 0.435 AC: 2103 AN: 4832

European-Finnish (FIN) AF: 0.315 AC: 3327 AN: 10566

Middle Eastern (MID) AF: 0.510 AC: 149 AN: 292

European-Non Finnish (NFE) AF: 0.332 AC: 22565 AN: 67976

Other (OTH) AF: 0.376 AC: 794 AN: 2110

Alfa AF: 0.339 Hom.: 4855

Bravo AF: 0.345

Asia WGS AF: 0.467 AC: 1624 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	13
DANN	Benign	0.71
PhyloP100		0.29

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs10495936;

hg19: chr2-46908199;