NM_199141.2:c.221-14382A>G

Variant names:

• chr19-10890569-A-G
• rs4804544
• NM_199141.2:c.221-14382A>G

Variant summary

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

The NM_199141.2(CARM1):​c.221-14382A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.292 in 150,560 control chromosomes in the GnomAD database, including 6,607 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 0.29 (6607 hom., cov: 28)
• Consequence: CARM1 NM_199141.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.40
• Publications: 7 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=-1.07).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.517 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_199141.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CARM1	NM_199141.2	MANE Select	c.221-14382A>G		intron	N/A	NP_954592.1	Q86X55-3
	CARM1	NM_001370088.1		c.221-14382A>G		intron	N/A	NP_001357017.1	Q86X55-1
	CARM1	NM_001370089.1		c.116-14382A>G		intron	N/A	NP_001357018.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CARM1	ENST00000327064.9	TSL:1 MANE Select	c.221-14382A>G		intron	N/A	ENSP00000325690.4	Q86X55-3
	CARM1	ENST00000586221.5	TSL:1	n.95-14382A>G		intron	N/A	ENSP00000467746.1	K7EQA8
	CARM1	ENST00000710361.1		c.272-14382A>G		intron	N/A	ENSP00000518232.1	A0AA34QVH5

Frequencies

GnomAD3 genomes AF: 0.292 AC: 43871 AN: 150456 Hom.: 6583 Cov.: 28

Gnomad AFR AF: 0.264

Gnomad AMI AF: 0.343

Gnomad AMR AF: 0.264

Gnomad ASJ AF: 0.294

Gnomad EAS AF: 0.533

Gnomad SAS AF: 0.287

Gnomad FIN AF: 0.318

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.292

Gnomad OTH AF: 0.280

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

GnomAD4 genome AF: 0.292 AC: 43933 AN: 150560 Hom.: 6607 Cov.: 28 AF XY: 0.295 AC XY: 21667 AN XY: 73510

African (AFR) AF: 0.264 AC: 10869 AN: 41114

American (AMR) AF: 0.265 AC: 3999 AN: 15106

Ashkenazi Jewish (ASJ) AF: 0.294 AC: 1019 AN: 3466

East Asian (EAS) AF: 0.533 AC: 2729 AN: 5118

South Asian (SAS) AF: 0.288 AC: 1380 AN: 4792

European-Finnish (FIN) AF: 0.318 AC: 3162 AN: 9958

Middle Eastern (MID) AF: 0.354 AC: 104 AN: 294

European-Non Finnish (NFE) AF: 0.292 AC: 19773 AN: 67710

Other (OTH) AF: 0.280 AC: 587 AN: 2094

Alfa AF: 0.288 Hom.: 1001

Bravo AF: 0.290

Asia WGS AF: 0.346 AC: 1201 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.32
DANN	Benign	0.13
PhyloP100		-3.4
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: rs4804544; hg19: chr19-11001245;