2-36520513-T-C

Variant names:

• chr2-36520513-T-C
• rs848523
• NM_016441.3:c.2207-1579T>C

Variant summary

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

The NM_016441.3(CRIM1):​c.2207-1579T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.467 in 152,062 control chromosomes in the GnomAD database, including 17,256 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 0.47 (17256 hom., cov: 32)
• Consequence: CRIM1 NM_016441.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.28
• Publications: 5 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 = 0.799 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CRIM1	NM_016441.3	c.2207-1579T>C		intron_variant	Intron 12 of 16	ENST00000280527.7	NP_057525.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CRIM1	ENST00000280527.7	c.2207-1579T>C		intron_variant	Intron 12 of 16	1	NM_016441.3	ENSP00000280527.2
CRIM1	ENST00000413985.1	c.293-1579T>C		intron_variant	Intron 2 of 3	3		ENSP00000403120.1

Frequencies

GnomAD3 genomes AF: 0.467 AC: 70959 AN: 151944 Hom.: 17229 Cov.: 32

Gnomad AFR AF: 0.460

Gnomad AMI AF: 0.301

Gnomad AMR AF: 0.568

Gnomad ASJ AF: 0.335

Gnomad EAS AF: 0.820

Gnomad SAS AF: 0.603

Gnomad FIN AF: 0.392

Gnomad MID AF: 0.358

Gnomad NFE AF: 0.434

Gnomad OTH AF: 0.457

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

GnomAD4 genome AF: 0.467 AC: 71019 AN: 152062 Hom.: 17256 Cov.: 32 AF XY: 0.471 AC XY: 35017 AN XY: 74322

African (AFR) AF: 0.460 AC: 19068 AN: 41472

American (AMR) AF: 0.568 AC: 8684 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.335 AC: 1162 AN: 3468

East Asian (EAS) AF: 0.820 AC: 4239 AN: 5170

South Asian (SAS) AF: 0.604 AC: 2909 AN: 4818

European-Finnish (FIN) AF: 0.392 AC: 4148 AN: 10574

Middle Eastern (MID) AF: 0.350 AC: 103 AN: 294

European-Non Finnish (NFE) AF: 0.434 AC: 29467 AN: 67968

Other (OTH) AF: 0.459 AC: 965 AN: 2104

Alfa AF: 0.456 Hom.: 30587

Bravo AF: 0.481

Asia WGS AF: 0.661 AC: 2294 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.94
DANN	Benign	0.22
PhyloP100		-1.3
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: rs848523; hg19: chr2-36747656;