chr2-36453705-A-G

Variant names:

• chr2-36453705-A-G
• rs711254
• NM_016441.3:c.870-10829A>G

Variant summary

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

The NM_016441.3(CRIM1):​c.870-10829A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.759 in 152,196 control chromosomes in the GnomAD database, including 44,421 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 0.76 (44421 hom., cov: 33)
• Consequence: CRIM1 NM_016441.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.922
• Publications: 3 publications found

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]

CRIM1 Gene-Disease associations (from GenCC):

• colobomatous macrophthalmia-microcornea syndrome

  Inheritance: AD, Unknown Classification: SUPPORTIVE, LIMITED Submitted by: Orphanet, Labcorp Genetics (formerly Invitae)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.867 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016441.3. 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
	CRIM1	NM_016441.3	MANE Select	c.870-10829A>G		intron	N/A	NP_057525.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CRIM1	ENST00000280527.7	TSL:1 MANE Select	c.870-10829A>G		intron	N/A	ENSP00000280527.2
	CRIM1	ENST00000928039.1		c.993-10829A>G		intron	N/A	ENSP00000598098.1
	CRIM1	ENST00000868088.1		c.870-10829A>G		intron	N/A	ENSP00000538147.1

Frequencies

GnomAD3 genomes AF: 0.759 AC: 115437 AN: 152078 Hom.: 44376 Cov.: 33

Gnomad AFR AF: 0.875

Gnomad AMI AF: 0.807

Gnomad AMR AF: 0.773

Gnomad ASJ AF: 0.752

Gnomad EAS AF: 0.888

Gnomad SAS AF: 0.775

Gnomad FIN AF: 0.748

Gnomad MID AF: 0.703

Gnomad NFE AF: 0.677

Gnomad OTH AF: 0.728

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

GnomAD4 genome AF: 0.759 AC: 115542 AN: 152196 Hom.: 44421 Cov.: 33 AF XY: 0.765 AC XY: 56892 AN XY: 74406

African (AFR) AF: 0.875 AC: 36350 AN: 41544

American (AMR) AF: 0.773 AC: 11825 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.752 AC: 2606 AN: 3466

East Asian (EAS) AF: 0.888 AC: 4598 AN: 5176

South Asian (SAS) AF: 0.774 AC: 3740 AN: 4830

European-Finnish (FIN) AF: 0.748 AC: 7914 AN: 10584

Middle Eastern (MID) AF: 0.707 AC: 208 AN: 294

European-Non Finnish (NFE) AF: 0.677 AC: 46023 AN: 67988

Other (OTH) AF: 0.730 AC: 1542 AN: 2112

Alfa AF: 0.705 Hom.: 65716

Bravo AF: 0.769

Asia WGS AF: 0.831 AC: 2892 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.15
DANN	Benign	0.49
PhyloP100		-0.92
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs711254; hg19: chr2-36680848;