2-36448387-A-G

Position:

• chr2-36448387-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.869+5652A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.753 in 152,142 control chromosomes in the GnomAD database, including 43,523 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 0.75 (43523 hom., cov: 32)
• Consequence: CRIM1 NM_016441.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.441

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 = 0.876 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CRIM1	NM_016441.3	c.869+5652A>G		intron_variant		ENST00000280527.7	NP_057525.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CRIM1	ENST00000280527.7	c.869+5652A>G		intron_variant		1	NM_016441.3	ENSP00000280527.2
CRIM1	ENST00000426856.1	c.545+5652A>G		intron_variant		3		ENSP00000407636.1

Frequencies

GnomAD3 genomes AF: 0.753 AC: 114496 AN: 152024 Hom.: 43484 Cov.: 32

Gnomad AFR AF: 0.839

Gnomad AMI AF: 0.819

Gnomad AMR AF: 0.774

Gnomad ASJ AF: 0.749

Gnomad EAS AF: 0.898

Gnomad SAS AF: 0.774

Gnomad FIN AF: 0.759

Gnomad MID AF: 0.703

Gnomad NFE AF: 0.683

Gnomad OTH AF: 0.724

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

GnomAD4 genome AF: 0.753 AC: 114592 AN: 152142 Hom.: 43523 Cov.: 32 AF XY: 0.759 AC XY: 56490 AN XY: 74382

Gnomad4 AFR AF: 0.839

Gnomad4 AMR AF: 0.774

Gnomad4 ASJ AF: 0.749

Gnomad4 EAS AF: 0.898

Gnomad4 SAS AF: 0.773

Gnomad4 FIN AF: 0.759

Gnomad4 NFE AF: 0.683

Gnomad4 OTH AF: 0.726

Alfa AF: 0.704 Hom.: 21582

Bravo AF: 0.760

Asia WGS AF: 0.834 AC: 2902 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	0.025
DANN	Benign	0.58

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: rs848512; hg19: chr2-36675530;