14-105479046-C-T

Variant names:

• chr14-105479046-C-T
• rs781981653
• NM_001312.4:c.405C>T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 0P and 3B. BP4_Moderate BP7

The NM_001312.4(CRIP2):​c.405C>T​(p.Phe135Phe) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000375 in 1,574,436 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000034 (0 hom.)
• Consequence: CRIP2 NM_001312.4 splice_region, synonymous
• Scores: Splicing: ADA: 0.0001839
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.84
• Publications: 0 publications found

Genes affected

CRIP2 (HGNC:2361): (cysteine rich protein 2) This gene encodes a putative transcription factor with two LIM zinc-binding domains. The encoded protein may participate in the differentiation of smooth muscle tissue. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2012]

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.027).
• BP7: Synonymous conserved (PhyloP=-2.84 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001312.4. 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
	CRIP2	NM_001312.4	MANE Select	c.405C>T	p.Phe135Phe	splice_region synonymous	Exon 5 of 8	NP_001303.1	P52943-1
	CRIP2	NM_001270837.2		c.627C>T	p.Phe209Phe	splice_region synonymous	Exon 5 of 8	NP_001257766.1	P52943-2
	CRIP2	NM_001270841.2		c.44-79C>T		intron	N/A	NP_001257770.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CRIP2	ENST00000329146.9	TSL:1 MANE Select	c.405C>T	p.Phe135Phe	splice_region synonymous	Exon 5 of 8	ENSP00000328521.5	P52943-1
	CRIP2	ENST00000548309.1	TSL:1	n.1200C>T		splice_region non_coding_transcript_exon	Exon 5 of 8
	CRIP2	ENST00000483017.7	TSL:2	c.627C>T	p.Phe209Phe	splice_region synonymous	Exon 5 of 8	ENSP00000426119.2	P52943-2

Frequencies

GnomAD3 genomes AF: 0.0000659 AC: 10 AN: 151792 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000590

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000194

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000233 AC: 41 AN: 175610 AF XY: 0.000167

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00146

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000344 AC: 49 AN: 1422644 Hom.: 0 Cov.: 44 AF XY: 0.0000284 AC XY: 20 AN XY: 704212

African (AFR) AF: 0.00 AC: 0 AN: 32726

American (AMR) AF: 0.00111 AC: 44 AN: 39736

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25374

East Asian (EAS) AF: 0.00 AC: 0 AN: 37832

South Asian (SAS) AF: 0.00 AC: 0 AN: 81374

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48450

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4158

European-Non Finnish (NFE) AF: 0.00000457 AC: 5 AN: 1094184

Other (OTH) AF: 0.00 AC: 0 AN: 58810

GnomAD4 genome AF: 0.0000659 AC: 10 AN: 151792 Hom.: 0 Cov.: 32 AF XY: 0.0000540 AC XY: 4 AN XY: 74136

African (AFR) AF: 0.00 AC: 0 AN: 41352

American (AMR) AF: 0.000590 AC: 9 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3462

East Asian (EAS) AF: 0.000194 AC: 1 AN: 5144

South Asian (SAS) AF: 0.00 AC: 0 AN: 4814

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10576

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 312

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67874

Other (OTH) AF: 0.00 AC: 0 AN: 2084

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000680

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	0.33
DANN	Benign	0.91
PhyloP100		-2.8

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00018
dbscSNV1_RF	Benign	0.29
SpliceAI score (max)		0.030		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: rs781981653; hg19: chr14-105945383;