rs41291957

Positions:

• chr5-149428827-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NR_105059.1(CARMN):​n.728-56G>A variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.125 in 457,350 control chromosomes in the GnomAD database, including 4,704 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 0.12 (1556 hom., cov: 32)
  • Exomes 𝑓: 0.13 (3148 hom.)
• Consequence: CARMN NR_105059.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0550

Genes affected

CARMN (HGNC:42872): (cardiac mesoderm enhancer-associated non-coding RNA) Predicted to be involved in regulation of gene expression. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.297 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CARMN	NR_105059.1	n.728-56G>A		intron_variant, non_coding_transcript_variant
CARMN	NR_105060.1	n.664-56G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CARMN	ENST00000602315.2	n.629-56G>A		intron_variant, non_coding_transcript_variant		5
CARMN	ENST00000656891.1	n.478-56G>A		intron_variant, non_coding_transcript_variant
CARMN	ENST00000686037.1	n.631-56G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.119 AC: 18146 AN: 152108 Hom.: 1556 Cov.: 32

Gnomad AFR AF: 0.0290

Gnomad AMI AF: 0.310

Gnomad AMR AF: 0.0888

Gnomad ASJ AF: 0.0845

Gnomad EAS AF: 0.311

Gnomad SAS AF: 0.0685

Gnomad FIN AF: 0.269

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.147

Gnomad OTH AF: 0.0950

GnomAD4 exome AF: 0.128 AC: 39185 AN: 305122 Hom.: 3148 Cov.: 0 AF XY: 0.123 AC XY: 21202 AN XY: 172984

Gnomad4 AFR exome AF: 0.0273

Gnomad4 AMR exome AF: 0.0865

Gnomad4 ASJ exome AF: 0.0814

Gnomad4 EAS exome AF: 0.308

Gnomad4 SAS exome AF: 0.0628

Gnomad4 FIN exome AF: 0.254

Gnomad4 NFE exome AF: 0.142

Gnomad4 OTH exome AF: 0.130

GnomAD4 genome AF: 0.119 AC: 18155 AN: 152228 Hom.: 1556 Cov.: 32 AF XY: 0.126 AC XY: 9349 AN XY: 74422

Gnomad4 AFR AF: 0.0289

Gnomad4 AMR AF: 0.0885

Gnomad4 ASJ AF: 0.0845

Gnomad4 EAS AF: 0.310

Gnomad4 SAS AF: 0.0688

Gnomad4 FIN AF: 0.269

Gnomad4 NFE AF: 0.147

Gnomad4 OTH AF: 0.102

Alfa AF: 0.134 Hom.: 327

Bravo AF: 0.104

Asia WGS AF: 0.191 AC: 664 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.5
DANN	Benign	0.33

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs41291957; hg19: chr5-148808390; COSMIC: COSV66047168;