rs1541596

Positions:

• chr19-10876337-A-G

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
CARM1	NM_199141.2	c.220+4415A>G		intron_variant		ENST00000327064.9	NP_954592.1
CARM1	NM_001370088.1	c.220+4415A>G		intron_variant			NP_001357017.1
CARM1	NM_001370089.1	c.115+3745A>G		intron_variant			NP_001357018.1
CARM1	XM_047438058.1	c.115+3745A>G		intron_variant			XP_047294014.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CARM1	ENST00000327064.9	c.220+4415A>G		intron_variant		1	NM_199141.2	ENSP00000325690	P2

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

Gnomad4 AFR AF: 0.728

Gnomad4 AMR AF: 0.462

Gnomad4 ASJ AF: 0.539

Gnomad4 EAS AF: 0.751

Gnomad4 SAS AF: 0.513

Gnomad4 FIN AF: 0.526

Gnomad4 NFE AF: 0.510

Gnomad4 OTH AF: 0.572

Alfa AF: 0.523 Hom.: 30010

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs1541596; hg19: chr19-10987013;