NM_199141.2:c.220+4415A>G

Variant names:

• chr19-10876337-A-G
• rs1541596
• NM_199141.2:c.220+4415A>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.220+4415A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.576 in 152,166 control chromosomes in the GnomAD database, including 26,022 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 0.58 (26022 hom., cov: 34)
• Consequence: CARM1 NM_199141.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.33
• Publications: 13 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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.731 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CARM1	NM_199141.2	c.220+4415A>G		intron_variant	Intron 1 of 15	ENST00000327064.9	NP_954592.1
CARM1	NM_001370088.1	c.220+4415A>G		intron_variant	Intron 1 of 14		NP_001357017.1
CARM1	NM_001370089.1	c.115+3745A>G		intron_variant	Intron 1 of 14		NP_001357018.1
CARM1	XM_047438058.1	c.115+3745A>G		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.220+4415A>G		intron_variant	Intron 1 of 15	1	NM_199141.2	ENSP00000325690.4

Frequencies

GnomAD3 genomes AF: 0.575 AC: 87447 AN: 152048 Hom.: 25948 Cov.: 34

Gnomad AFR AF: 0.727

Gnomad AMI AF: 0.454

Gnomad AMR AF: 0.462

Gnomad ASJ AF: 0.539

Gnomad EAS AF: 0.750

Gnomad SAS AF: 0.514

Gnomad FIN AF: 0.526

Gnomad MID AF: 0.636

Gnomad NFE AF: 0.510

Gnomad OTH AF: 0.569

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

GnomAD4 genome AF: 0.576 AC: 87580 AN: 152166 Hom.: 26022 Cov.: 34 AF XY: 0.573 AC XY: 42645 AN XY: 74380

African (AFR) AF: 0.728 AC: 30206 AN: 41514

American (AMR) AF: 0.462 AC: 7074 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.539 AC: 1873 AN: 3472

East Asian (EAS) AF: 0.751 AC: 3882 AN: 5170

South Asian (SAS) AF: 0.513 AC: 2480 AN: 4830

European-Finnish (FIN) AF: 0.526 AC: 5561 AN: 10566

Middle Eastern (MID) AF: 0.643 AC: 189 AN: 294

European-Non Finnish (NFE) AF: 0.510 AC: 34693 AN: 68002

Other (OTH) AF: 0.572 AC: 1209 AN: 2112

Alfa AF: 0.527 Hom.: 48466

Bravo AF: 0.582

Asia WGS AF: 0.623 AC: 2167 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.81
DANN	Benign	0.25
PhyloP100		-2.3
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: rs1541596; hg19: chr19-10987013;