14-105478821-C-T

Variant names:

• chr14-105478821-C-T
• rs904360907
• NM_001312.4:c.287C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001312.4(CRIP2):​c.287C>T​(p.Ala96Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000028 in 1,430,982 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A96G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000023 (0 hom.)
• Consequence: CRIP2 NM_001312.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.244
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.093559116).

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.287C>T	p.Ala96Val	missense	Exon 4 of 8	NP_001303.1	P52943-1
	CRIP2	NM_001270837.2		c.509C>T	p.Ala170Val	missense	Exon 4 of 8	NP_001257766.1	P52943-2
	CRIP2	NM_001270841.2		c.44-304C>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.287C>T	p.Ala96Val	missense	Exon 4 of 8	ENSP00000328521.5	P52943-1
	CRIP2	ENST00000548309.1	TSL:1	n.1082C>T		non_coding_transcript_exon	Exon 4 of 8
	CRIP2	ENST00000483017.7	TSL:2	c.509C>T	p.Ala170Val	missense	Exon 4 of 8	ENSP00000426119.2	P52943-2

Frequencies

GnomAD3 genomes AF: 0.00000659 AC: 1 AN: 151816 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

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

GnomAD4 exome AF: 0.00000235 AC: 3 AN: 1279166 Hom.: 0 Cov.: 38 AF XY: 0.00 AC XY: 0 AN XY: 623012

African (AFR) AF: 0.0000778 AC: 2 AN: 25722

American (AMR) AF: 0.00 AC: 0 AN: 18434

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18516

East Asian (EAS) AF: 0.00 AC: 0 AN: 32798

South Asian (SAS) AF: 0.00 AC: 0 AN: 62278

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 30958

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3596

European-Non Finnish (NFE) AF: 9.67e-7 AC: 1 AN: 1033814

Other (OTH) AF: 0.00 AC: 0 AN: 53050

GnomAD4 genome AF: 0.00000659 AC: 1 AN: 151816 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74156

African (AFR) AF: 0.0000242 AC: 1 AN: 41362

American (AMR) AF: 0.00 AC: 0 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5112

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10592

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67896

Other (OTH) AF: 0.00 AC: 0 AN: 2080

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000189

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.067
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	8.8
DANN	Uncertain	0.99
DEOGEN2	Benign	0.065	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.094	N
LIST_S2	Benign	0.64	T
M_CAP	Uncertain	0.21	D
MetaRNN	Benign	0.094	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.76	N
PhyloP100		0.24
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	-0.49	N
REVEL	Benign	0.059
Sift	Benign	0.11	T
Sift4G	Benign	0.13	T
Polyphen		0.0	B
Vest4		0.033
MutPred		0.23		Gain of catalytic residue at I91 (P = 0.1308)
MVP		0.56
MPC		0.24
ClinPred		0.059	T
GERP RS		-0.10
Varity_R		0.030
gMVP		0.26
Mutation Taster		=93/7	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
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: rs904360907; hg19: chr14-105945158;