rs3087822

Variant names:

• chr2-46624894-A-G
• rs3087822
• NM_014171.6:c.*667A>G

Variant summary

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

The NM_014171.6(CRIPT):​c.*667A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.507 in 151,664 control chromosomes in the GnomAD database, including 21,144 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 0.51 (21144 hom., cov: 30)
  • Exomes 𝑓: 0.50 (0 hom.)
• Consequence: CRIPT NM_014171.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.932

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=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.715 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CRIPT	NM_014171.6	c.*667A>G		3_prime_UTR_variant	Exon 5 of 5	ENST00000238892.4	NP_054890.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CRIPT	ENST00000238892.4	c.*667A>G		3_prime_UTR_variant	Exon 5 of 5	1	NM_014171.6	ENSP00000238892.3
CRIPT	ENST00000486447.1	n.1565A>G		non_coding_transcript_exon_variant	Exon 5 of 5	5

Frequencies

GnomAD3 genomes AF: 0.507 AC: 76826 AN: 151544 Hom.: 21101 Cov.: 30

Gnomad AFR AF: 0.721

Gnomad AMI AF: 0.498

Gnomad AMR AF: 0.494

Gnomad ASJ AF: 0.510

Gnomad EAS AF: 0.162

Gnomad SAS AF: 0.478

Gnomad FIN AF: 0.327

Gnomad MID AF: 0.487

Gnomad NFE AF: 0.438

Gnomad OTH AF: 0.473

GnomAD4 exome AF: 0.500 AC: 1 AN: 2 Hom.: 0 Cov.: 0 AF XY: 0.500 AC XY: 1 AN XY: 2

Gnomad4 NFE exome AF: 0.500

GnomAD4 genome AF: 0.507 AC: 76919 AN: 151662 Hom.: 21144 Cov.: 30 AF XY: 0.500 AC XY: 37068 AN XY: 74120

Gnomad4 AFR AF: 0.722

Gnomad4 AMR AF: 0.494

Gnomad4 ASJ AF: 0.510

Gnomad4 EAS AF: 0.162

Gnomad4 SAS AF: 0.477

Gnomad4 FIN AF: 0.327

Gnomad4 NFE AF: 0.437

Gnomad4 OTH AF: 0.467

Alfa AF: 0.459 Hom.: 17354

Bravo AF: 0.523

Asia WGS AF: 0.351 AC: 1222 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.28
DANN	Benign	0.79

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: rs3087822; hg19: chr2-46852033;