2-36446412-T-G

Variant names:

• chr2-36446412-T-G
• rs7562790
• NM_016441.3:c.869+3677T>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.869+3677T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.478 in 152,058 control chromosomes in the GnomAD database, including 17,909 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 0.48 (17909 hom., cov: 32)
• Consequence: CRIM1 NM_016441.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.50
• Publications: 28 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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.596 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.869+3677T>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.869+3677T>G		intron	N/A	ENSP00000280527.2	Q9NZV1
	CRIM1	ENST00000928039.1		c.992+3677T>G		intron	N/A	ENSP00000598098.1
	CRIM1	ENST00000868088.1		c.869+3677T>G		intron	N/A	ENSP00000538147.1

Frequencies

GnomAD3 genomes AF: 0.478 AC: 72588 AN: 151938 Hom.: 17893 Cov.: 32

Gnomad AFR AF: 0.597

Gnomad AMI AF: 0.412

Gnomad AMR AF: 0.455

Gnomad ASJ AF: 0.410

Gnomad EAS AF: 0.614

Gnomad SAS AF: 0.588

Gnomad FIN AF: 0.426

Gnomad MID AF: 0.389

Gnomad NFE AF: 0.405

Gnomad OTH AF: 0.468

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

GnomAD4 genome AF: 0.478 AC: 72651 AN: 152058 Hom.: 17909 Cov.: 32 AF XY: 0.480 AC XY: 35666 AN XY: 74330

African (AFR) AF: 0.597 AC: 24758 AN: 41482

American (AMR) AF: 0.455 AC: 6963 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.410 AC: 1425 AN: 3472

East Asian (EAS) AF: 0.614 AC: 3166 AN: 5154

South Asian (SAS) AF: 0.587 AC: 2829 AN: 4820

European-Finnish (FIN) AF: 0.426 AC: 4505 AN: 10574

Middle Eastern (MID) AF: 0.391 AC: 115 AN: 294

European-Non Finnish (NFE) AF: 0.405 AC: 27524 AN: 67942

Other (OTH) AF: 0.468 AC: 991 AN: 2116

Alfa AF: 0.428 Hom.: 50494

Bravo AF: 0.483

Asia WGS AF: 0.611 AC: 2127 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.17
DANN	Benign	0.45
PhyloP100		-2.5
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: rs7562790; hg19: chr2-36673555;