rs11670365

Variant names:

• chr19-10894157-C-T
• rs11670365
• NM_199141.2:c.221-10794C>T

Variant summary

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

The NM_199141.2(CARM1):​c.221-10794C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.07 in 152,314 control chromosomes in the GnomAD database, including 401 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 0.070 (401 hom., cov: 32)
• Consequence: CARM1 NM_199141.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.113
• Publications: 9 publications found

Genes affected

CARM1 (HGNC:23393): (coactivator associated arginine methyltransferase 1) This gene belongs to the protein arginine methyltransferase (PRMT) family. The encoded enzyme catalyzes the methylation of guanidino nitrogens of arginyl residues of proteins. The enzyme acts specifically on histones and other chromatin-associated proteins and is involved in regulation of gene expression. The enzyme may act in association with other proteins or within multi-protein complexes and may play a role in cell type-specific functions and cell lineage specification. A related pseudogene is located on chromosome 9. [provided by RefSeq, Aug 2013]

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 (NFE) allele frequency at 95% confidence interval = 0.0817 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CARM1	NM_199141.2	c.221-10794C>T		intron_variant	Intron 1 of 15	ENST00000327064.9	NP_954592.1
CARM1	NM_001370088.1	c.221-10794C>T		intron_variant	Intron 1 of 14		NP_001357017.1
CARM1	NM_001370089.1	c.116-10794C>T		intron_variant	Intron 1 of 14		NP_001357018.1
CARM1	XM_047438058.1	c.116-10794C>T		intron_variant	Intron 1 of 15		XP_047294014.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CARM1	ENST00000327064.9	c.221-10794C>T		intron_variant	Intron 1 of 15	1	NM_199141.2	ENSP00000325690.4

Frequencies

GnomAD3 genomes AF: 0.0701 AC: 10664 AN: 152198 Hom.: 401 Cov.: 32

Gnomad AFR AF: 0.0553

Gnomad AMI AF: 0.0471

Gnomad AMR AF: 0.0517

Gnomad ASJ AF: 0.0554

Gnomad EAS AF: 0.0314

Gnomad SAS AF: 0.0838

Gnomad FIN AF: 0.0861

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.0835

Gnomad OTH AF: 0.0750

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

GnomAD4 genome AF: 0.0700 AC: 10666 AN: 152314 Hom.: 401 Cov.: 32 AF XY: 0.0688 AC XY: 5121 AN XY: 74486

African (AFR) AF: 0.0551 AC: 2292 AN: 41564

American (AMR) AF: 0.0517 AC: 791 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0554 AC: 192 AN: 3468

East Asian (EAS) AF: 0.0318 AC: 165 AN: 5182

South Asian (SAS) AF: 0.0834 AC: 403 AN: 4830

European-Finnish (FIN) AF: 0.0861 AC: 914 AN: 10612

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.0835 AC: 5683 AN: 68030

Other (OTH) AF: 0.0747 AC: 158 AN: 2116

Alfa AF: 0.0690 Hom.: 99

Bravo AF: 0.0667

Asia WGS AF: 0.0820 AC: 288 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	4.3
DANN	Benign	0.46
PhyloP100		-0.11
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: rs11670365; hg19: chr19-11004833;