NM_016441.3:c.2428+3666T>G

Variant names:

• chr2-36525979-T-G
• rs3821153
• NM_016441.3:c.2428+3666T>G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_016441.3(CRIM1):​c.2428+3666T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.419 in 152,014 control chromosomes in the GnomAD database, including 13,523 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 0.42 (13523 hom., cov: 32)
• Consequence: CRIM1 NM_016441.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.306
• Publications: 6 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.39).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.53 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CRIM1	NM_016441.3	MANE Select	c.2428+3666T>G		intron	N/A	NP_057525.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CRIM1	ENST00000280527.7	TSL:1 MANE Select	c.2428+3666T>G		intron	N/A	ENSP00000280527.2
	CRIM1	ENST00000413985.1	TSL:3	c.515-3174T>G		intron	N/A	ENSP00000403120.1

Frequencies

GnomAD3 genomes AF: 0.419 AC: 63592 AN: 151896 Hom.: 13511 Cov.: 32

Gnomad AFR AF: 0.418

Gnomad AMI AF: 0.300

Gnomad AMR AF: 0.384

Gnomad ASJ AF: 0.336

Gnomad EAS AF: 0.547

Gnomad SAS AF: 0.526

Gnomad FIN AF: 0.344

Gnomad MID AF: 0.334

Gnomad NFE AF: 0.428

Gnomad OTH AF: 0.395

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

GnomAD4 genome AF: 0.419 AC: 63646 AN: 152014 Hom.: 13523 Cov.: 32 AF XY: 0.416 AC XY: 30898 AN XY: 74326

African (AFR) AF: 0.418 AC: 17319 AN: 41442

American (AMR) AF: 0.384 AC: 5868 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.336 AC: 1166 AN: 3466

East Asian (EAS) AF: 0.547 AC: 2827 AN: 5168

South Asian (SAS) AF: 0.527 AC: 2537 AN: 4816

European-Finnish (FIN) AF: 0.344 AC: 3634 AN: 10566

Middle Eastern (MID) AF: 0.332 AC: 97 AN: 292

European-Non Finnish (NFE) AF: 0.428 AC: 29097 AN: 67954

Other (OTH) AF: 0.392 AC: 828 AN: 2110

Alfa AF: 0.411 Hom.: 7038

Bravo AF: 0.418

Asia WGS AF: 0.495 AC: 1718 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.39
CADD	Benign	15
DANN	Benign	0.73
PhyloP100		0.31
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs3821153; hg19: chr2-36753122;