rs884215

chr2-36515812-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_016441.3(CRIM1):c.1991-1515A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.366 in 152,136 control chromosomes in the GnomAD database, including 10,709 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 0.37 (10709 hom., cov: 33)
• Consequence: CRIM1 NM_016441.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.437

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.533 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CRIM1	NM_016441.3	c.1991-1515A>G		intron_variant		ENST00000280527.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CRIM1	ENST00000280527.7	c.1991-1515A>G		intron_variant		1	NM_016441.3	P1
CRIM1	ENST00000413985.1	c.77-1515A>G		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.366 AC: 55707 AN: 152018 Hom.: 10700 Cov.: 33

Gnomad AFR AF: 0.260

Gnomad AMI AF: 0.308

Gnomad AMR AF: 0.369

Gnomad ASJ AF: 0.320

Gnomad EAS AF: 0.549

Gnomad SAS AF: 0.493

Gnomad FIN AF: 0.376

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.410

Gnomad OTH AF: 0.354

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

GnomAD4 genome AF: 0.366 AC: 55737 AN: 152136 Hom.: 10709 Cov.: 33 AF XY: 0.367 AC XY: 27293 AN XY: 74392

Gnomad4 AFR AF: 0.260

Gnomad4 AMR AF: 0.369

Gnomad4 ASJ AF: 0.320

Gnomad4 EAS AF: 0.550

Gnomad4 SAS AF: 0.494

Gnomad4 FIN AF: 0.376

Gnomad4 NFE AF: 0.410

Gnomad4 OTH AF: 0.352

Alfa AF: 0.397 Hom.: 13350

Bravo AF: 0.358

Asia WGS AF: 0.488 AC: 1692 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	1.3
Dann	Benign	0.48

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

Publications

LitVar

Other links and lift over

dbSNP: rs884215; hg19: chr2-36742955;