19-10904261-C-T

Variant names:

• chr19-10904261-C-T
• rs12971616
• NM_199141.2:c.221-690C>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.221-690C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.215 in 152,238 control chromosomes in the GnomAD database, including 3,771 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 0.21 (3771 hom., cov: 33)
• Consequence: CARM1 NM_199141.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.22
• Publications: 6 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=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.264 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.221-690C>T		intron	N/A	NP_954592.1	Q86X55-3
	CARM1	NM_001370088.1		c.221-690C>T		intron	N/A	NP_001357017.1	Q86X55-1
	CARM1	NM_001370089.1		c.116-690C>T		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.221-690C>T		intron	N/A	ENSP00000325690.4	Q86X55-3
	CARM1	ENST00000586221.5	TSL:1	n.95-690C>T		intron	N/A	ENSP00000467746.1	K7EQA8
	CARM1	ENST00000710361.1		c.272-690C>T		intron	N/A	ENSP00000518232.1	A0AA34QVH5

Frequencies

GnomAD3 genomes AF: 0.215 AC: 32711 AN: 152120 Hom.: 3768 Cov.: 33

Gnomad AFR AF: 0.131

Gnomad AMI AF: 0.336

Gnomad AMR AF: 0.180

Gnomad ASJ AF: 0.267

Gnomad EAS AF: 0.179

Gnomad SAS AF: 0.251

Gnomad FIN AF: 0.231

Gnomad MID AF: 0.313

Gnomad NFE AF: 0.267

Gnomad OTH AF: 0.212

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

GnomAD4 genome AF: 0.215 AC: 32724 AN: 152238 Hom.: 3771 Cov.: 33 AF XY: 0.214 AC XY: 15937 AN XY: 74440

African (AFR) AF: 0.131 AC: 5447 AN: 41564

American (AMR) AF: 0.180 AC: 2751 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.267 AC: 928 AN: 3470

East Asian (EAS) AF: 0.179 AC: 928 AN: 5178

South Asian (SAS) AF: 0.251 AC: 1214 AN: 4830

European-Finnish (FIN) AF: 0.231 AC: 2452 AN: 10592

Middle Eastern (MID) AF: 0.313 AC: 92 AN: 294

European-Non Finnish (NFE) AF: 0.267 AC: 18156 AN: 67996

Other (OTH) AF: 0.213 AC: 450 AN: 2116

Alfa AF: 0.205 Hom.: 1700

Bravo AF: 0.207

Asia WGS AF: 0.193 AC: 673 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.40
DANN	Benign	0.37
PhyloP100		-1.2
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: rs12971616; hg19: chr19-11014937;