rs373748249

Variant names:

• chr2-36356357-G-C
• NM_016441.3:c.65G>C

Your query was ambiguous. Multiple possible variants found:

• chr2-36356357-G-C
• chr2-36356357-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_016441.3(CRIM1):​c.65G>C​(p.Gly22Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000694 in 1,440,688 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: CRIM1 NM_016441.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.161

Genes affected

CRIM1 (HGNC:2359): (cysteine rich transmembrane BMP regulator 1) This gene encodes a transmembrane protein containing six cysteine-rich repeat domains and an insulin-like growth factor-binding domain. The encoded protein may play a role in tissue development though interactions with members of the transforming growth factor beta family, such as bone morphogenetic proteins. [provided by RefSeq, Nov 2010]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.112026036).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CRIM1	NM_016441.3	c.65G>C	p.Gly22Ala	missense_variant	Exon 1 of 17	ENST00000280527.7	NP_057525.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CRIM1	ENST00000280527.7	c.65G>C	p.Gly22Ala	missense_variant	Exon 1 of 17	1	NM_016441.3	ENSP00000280527.2
CRIM1	ENST00000426856.1	c.-86G>C		upstream_gene_variant		3		ENSP00000407636.1
CRIM1	ENST00000428774.1	c.-116G>C		upstream_gene_variant		3		ENSP00000415706.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.94e-7 AC: 1 AN: 1440688 Hom.: 0 Cov.: 31 AF XY: 0.00000140 AC XY: 1 AN XY: 714972

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.06e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.070
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.059	T
Eigen	Benign	-0.55
Eigen_PC	Benign	-0.46
FATHMM_MKL	Benign	0.18	N
LIST_S2	Benign	0.73	T
M_CAP	Pathogenic	0.66	D
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	-0.20	N
PrimateAI	Pathogenic	0.90	D
PROVEAN	Benign	0.080	N
REVEL	Benign	0.036
Sift	Benign	1.0	T
Sift4G	Benign	0.81	T
Polyphen		0.063	B
Vest4		0.21
MutPred		0.45		Loss of helix (P = 0.0017);
MVP		0.32
MPC		0.28
ClinPred		0.098	T
GERP RS		0.65
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8
Varity_R		0.065
gMVP		0.43

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-36583500;