19-10891903-A-G

Variant names:

• chr19-10891903-A-G
• rs7254708
• NM_199141.2:c.221-13048A>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.221-13048A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.909 in 152,306 control chromosomes in the GnomAD database, including 63,202 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 0.91 (63202 hom., cov: 32)
• Consequence: CARM1 NM_199141.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.99
• 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=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CARM1	NM_199141.2	MANE Select	c.221-13048A>G		intron	N/A	NP_954592.1
	CARM1	NM_001370088.1		c.221-13048A>G		intron	N/A	NP_001357017.1
	CARM1	NM_001370089.1		c.116-13048A>G		intron	N/A	NP_001357018.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CARM1	ENST00000327064.9	TSL:1 MANE Select	c.221-13048A>G		intron	N/A	ENSP00000325690.4
	CARM1	ENST00000586221.5	TSL:1	n.95-13048A>G		intron	N/A	ENSP00000467746.1
	CARM1	ENST00000710361.1		c.272-13048A>G		intron	N/A	ENSP00000518232.1

Frequencies

GnomAD3 genomes AF: 0.909 AC: 138359 AN: 152188 Hom.: 63137 Cov.: 32

Gnomad AFR AF: 0.978

Gnomad AMI AF: 0.839

Gnomad AMR AF: 0.933

Gnomad ASJ AF: 0.852

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.962

Gnomad FIN AF: 0.868

Gnomad MID AF: 0.867

Gnomad NFE AF: 0.862

Gnomad OTH AF: 0.907

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

GnomAD4 genome AF: 0.909 AC: 138484 AN: 152306 Hom.: 63202 Cov.: 32 AF XY: 0.911 AC XY: 67854 AN XY: 74474

African (AFR) AF: 0.978 AC: 40642 AN: 41574

American (AMR) AF: 0.933 AC: 14260 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.852 AC: 2955 AN: 3470

East Asian (EAS) AF: 0.999 AC: 5171 AN: 5176

South Asian (SAS) AF: 0.962 AC: 4652 AN: 4834

European-Finnish (FIN) AF: 0.868 AC: 9222 AN: 10624

Middle Eastern (MID) AF: 0.874 AC: 257 AN: 294

European-Non Finnish (NFE) AF: 0.862 AC: 58642 AN: 68026

Other (OTH) AF: 0.908 AC: 1918 AN: 2112

Alfa AF: 0.909 Hom.: 9461

Bravo AF: 0.917

Asia WGS AF: 0.982 AC: 3415 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.79
DANN	Benign	0.53
PhyloP100		-2.0
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: rs7254708; hg19: chr19-11002579;