2-36451885-T-G

Variant names:

• chr2-36451885-T-G
• rs3770876
• NM_016441.3:c.869+9150T>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+9150T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.522 in 152,006 control chromosomes in the GnomAD database, including 22,505 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 0.52 (22505 hom., cov: 32)
• Consequence: CRIM1 NM_016441.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.212
• 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: 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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.735 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CRIM1	NM_016441.3	c.869+9150T>G		intron_variant	Intron 4 of 16	ENST00000280527.7	NP_057525.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CRIM1	ENST00000280527.7	c.869+9150T>G		intron_variant	Intron 4 of 16	1	NM_016441.3	ENSP00000280527.2
CRIM1	ENST00000426856.1	c.545+9150T>G		intron_variant	Intron 3 of 3	3		ENSP00000407636.1

Frequencies

GnomAD3 genomes AF: 0.522 AC: 79302 AN: 151888 Hom.: 22472 Cov.: 32

Gnomad AFR AF: 0.741

Gnomad AMI AF: 0.341

Gnomad AMR AF: 0.493

Gnomad ASJ AF: 0.411

Gnomad EAS AF: 0.691

Gnomad SAS AF: 0.636

Gnomad FIN AF: 0.419

Gnomad MID AF: 0.415

Gnomad NFE AF: 0.400

Gnomad OTH AF: 0.500

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

GnomAD4 genome AF: 0.522 AC: 79398 AN: 152006 Hom.: 22505 Cov.: 32 AF XY: 0.525 AC XY: 38968 AN XY: 74294

African (AFR) AF: 0.741 AC: 30736 AN: 41452

American (AMR) AF: 0.493 AC: 7531 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.411 AC: 1426 AN: 3470

East Asian (EAS) AF: 0.692 AC: 3571 AN: 5164

South Asian (SAS) AF: 0.635 AC: 3059 AN: 4818

European-Finnish (FIN) AF: 0.419 AC: 4417 AN: 10552

Middle Eastern (MID) AF: 0.425 AC: 125 AN: 294

European-Non Finnish (NFE) AF: 0.400 AC: 27170 AN: 67956

Other (OTH) AF: 0.500 AC: 1053 AN: 2106

Alfa AF: 0.431 Hom.: 41593

Bravo AF: 0.534

Asia WGS AF: 0.677 AC: 2354 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.0
DANN	Benign	0.45
PhyloP100		-0.21
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: rs3770876; hg19: chr2-36679028;