2-36391524-A-G

Variant names:

• chr2-36391524-A-G
• rs11124513
• NM_016441.3:c.332-5090A>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.332-5090A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.377 in 151,842 control chromosomes in the GnomAD database, including 11,946 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 0.38 (11946 hom., cov: 30)
• Consequence: CRIM1 NM_016441.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.461
• Publications: 2 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.562 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.332-5090A>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.332-5090A>G		intron	N/A	ENSP00000280527.2	Q9NZV1
	CRIM1	ENST00000928039.1		c.455-5090A>G		intron	N/A	ENSP00000598098.1
	CRIM1	ENST00000868088.1		c.332-5090A>G		intron	N/A	ENSP00000538147.1

Frequencies

GnomAD3 genomes AF: 0.377 AC: 57145 AN: 151724 Hom.: 11922 Cov.: 30

Gnomad AFR AF: 0.568

Gnomad AMI AF: 0.377

Gnomad AMR AF: 0.397

Gnomad ASJ AF: 0.295

Gnomad EAS AF: 0.362

Gnomad SAS AF: 0.332

Gnomad FIN AF: 0.297

Gnomad MID AF: 0.363

Gnomad NFE AF: 0.278

Gnomad OTH AF: 0.345

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

GnomAD4 genome AF: 0.377 AC: 57226 AN: 151842 Hom.: 11946 Cov.: 30 AF XY: 0.378 AC XY: 28050 AN XY: 74200

African (AFR) AF: 0.568 AC: 23477 AN: 41340

American (AMR) AF: 0.397 AC: 6044 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.295 AC: 1024 AN: 3468

East Asian (EAS) AF: 0.362 AC: 1873 AN: 5170

South Asian (SAS) AF: 0.332 AC: 1600 AN: 4816

European-Finnish (FIN) AF: 0.297 AC: 3127 AN: 10518

Middle Eastern (MID) AF: 0.377 AC: 110 AN: 292

European-Non Finnish (NFE) AF: 0.278 AC: 18898 AN: 67984

Other (OTH) AF: 0.347 AC: 731 AN: 2108

Alfa AF: 0.295 Hom.: 20127

Bravo AF: 0.396

Asia WGS AF: 0.367 AC: 1276 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.30
DANN	Benign	0.60
PhyloP100		-0.46
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: rs11124513; hg19: chr2-36618667;