2-36525979-T-G

Variant summary

Our verdict is Benign. Variant got -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

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 -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CRIM1	NM_016441.3	c.2428+3666T>G		intron_variant		ENST00000280527.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CRIM1	ENST00000280527.7	c.2428+3666T>G		intron_variant		1	NM_016441.3	P1
CRIM1	ENST00000413985.1	c.515-3174T>G		intron_variant		3

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

Gnomad4 AFR AF: 0.418

Gnomad4 AMR AF: 0.384

Gnomad4 ASJ AF: 0.336

Gnomad4 EAS AF: 0.547

Gnomad4 SAS AF: 0.527

Gnomad4 FIN AF: 0.344

Gnomad4 NFE AF: 0.428

Gnomad4 OTH AF: 0.392

Alfa AF: 0.409 Hom.: 6251

Bravo AF: 0.418

Asia WGS AF: 0.495 AC: 1718 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.39
Cadd	Benign	15
Dann	Benign	0.73
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs3821153; hg19: chr2-36753122;