rs884215

Variant names:

• chr2-36515812-A-G
• rs884215
• NM_016441.3:c.1991-1515A>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.1991-1515A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.366 in 152,136 control chromosomes in the GnomAD database, including 10,709 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 0.37 (10709 hom., cov: 33)
• Consequence: CRIM1 NM_016441.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.437
• Publications: 4 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: Unknown, AD Classification: SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.533 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.1991-1515A>G		intron	N/A	NP_057525.1	Q9NZV1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CRIM1	ENST00000280527.7	TSL:1 MANE Select	c.1991-1515A>G		intron	N/A	ENSP00000280527.2	Q9NZV1
	CRIM1	ENST00000928039.1		c.2114-1515A>G		intron	N/A	ENSP00000598098.1
	CRIM1	ENST00000868088.1		c.1991-1515A>G		intron	N/A	ENSP00000538147.1

Frequencies

GnomAD3 genomes AF: 0.366 AC: 55707 AN: 152018 Hom.: 10700 Cov.: 33

Gnomad AFR AF: 0.260

Gnomad AMI AF: 0.308

Gnomad AMR AF: 0.369

Gnomad ASJ AF: 0.320

Gnomad EAS AF: 0.549

Gnomad SAS AF: 0.493

Gnomad FIN AF: 0.376

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.410

Gnomad OTH AF: 0.354

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

GnomAD4 genome AF: 0.366 AC: 55737 AN: 152136 Hom.: 10709 Cov.: 33 AF XY: 0.367 AC XY: 27293 AN XY: 74392

African (AFR) AF: 0.260 AC: 10789 AN: 41504

American (AMR) AF: 0.369 AC: 5645 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.320 AC: 1112 AN: 3470

East Asian (EAS) AF: 0.550 AC: 2841 AN: 5170

South Asian (SAS) AF: 0.494 AC: 2382 AN: 4820

European-Finnish (FIN) AF: 0.376 AC: 3978 AN: 10582

Middle Eastern (MID) AF: 0.265 AC: 78 AN: 294

European-Non Finnish (NFE) AF: 0.410 AC: 27888 AN: 67976

Other (OTH) AF: 0.352 AC: 744 AN: 2112

Alfa AF: 0.386 Hom.: 23385

Bravo AF: 0.358

Asia WGS AF: 0.488 AC: 1692 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.3
DANN	Benign	0.48
PhyloP100		-0.44
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs884215;

hg19: chr2-36742955;