rs11667234

Positions:

• chr19-10908905-C-A
• chr19-10908905-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_199141.2(CARM1):​c.454-198C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0268 in 152,316 control chromosomes in the GnomAD database, including 79 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 0.027 (79 hom., cov: 32)
• Consequence: CARM1 NM_199141.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.84

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=-0.91).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0268 (4084/152316) while in subpopulation NFE AF= 0.0416 (2832/68018). AF 95% confidence interval is 0.0404. There are 79 homozygotes in gnomad4. There are 1786 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 4084 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CARM1	NM_199141.2	c.454-198C>A		intron_variant		ENST00000327064.9	NP_954592.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CARM1	ENST00000327064.9	c.454-198C>A		intron_variant		1	NM_199141.2	ENSP00000325690.4

Frequencies

GnomAD3 genomes AF: 0.0268 AC: 4085 AN: 152198 Hom.: 79 Cov.: 32

Gnomad AFR AF: 0.0133

Gnomad AMI AF: 0.0197

Gnomad AMR AF: 0.0240

Gnomad ASJ AF: 0.0164

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00249

Gnomad FIN AF: 0.0168

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0416

Gnomad OTH AF: 0.0297

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

GnomAD4 genome AF: 0.0268 AC: 4084 AN: 152316 Hom.: 79 Cov.: 32 AF XY: 0.0240 AC XY: 1786 AN XY: 74484

Gnomad4 AFR AF: 0.0132

Gnomad4 AMR AF: 0.0240

Gnomad4 ASJ AF: 0.0164

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00249

Gnomad4 FIN AF: 0.0168

Gnomad4 NFE AF: 0.0416

Gnomad4 OTH AF: 0.0294

Alfa AF: 0.0331 Hom.: 97

Bravo AF: 0.0264

Asia WGS AF: 0.00346 AC: 12 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.038
DANN	Benign	0.82

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs11667234; hg19: chr19-11019581;