19-5914958-C-A

Variant names:

• chr19-5914958-C-A
• rs768276521
• NM_004058.5:c.280C>A

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_004058.5(CAPS):​c.280C>A​(p.Arg94Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000351 in 1,453,968 control chromosomes in the GnomAD database, including 1 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: not found (cov: 33)
  • Exomes 𝑓: 0.000035 (1 hom.)
• Consequence: CAPS NM_004058.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.764
• Publications: 0 publications found

Genes affected

CAPS (HGNC:1487): (calcyphosine) This gene encodes a calcium-binding protein, which may play a role in the regulation of ion transport. A similar protein was first described as a potentially important regulatory protein in the dog thyroid and was termed as R2D5 antigen in rabbit. Alternative splicing of this gene generates two transcript variants. [provided by RefSeq, Jul 2008]

ENSG00000267571 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.31).
• BP7: Synonymous conserved (PhyloP=0.764 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004058.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CAPS	NM_004058.5	MANE Select	c.280C>A	p.Arg94Arg	synonymous	Exon 4 of 5	NP_004049.3	Q13938-4
	CAPS	NM_080590.4		c.280C>A	p.Arg94Arg	synonymous	Exon 4 of 5	NP_542157.3	A0A499FJ41

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CAPS	ENST00000588776.8	TSL:1 MANE Select	c.280C>A	p.Arg94Arg	synonymous	Exon 4 of 5	ENSP00000465883.2	Q13938-4
	CAPS	ENST00000585541.1	TSL:1	n.612C>A		non_coding_transcript_exon	Exon 2 of 2
	CAPS	ENST00000961097.1		c.280C>A	p.Arg94Arg	synonymous	Exon 4 of 5	ENSP00000631156.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.0000622 AC: 15 AN: 241006 AF XY: 0.0000683

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000295

Gnomad NFE exome AF: 0.0000823

Gnomad OTH exome AF: 0.000166

GnomAD4 exome AF: 0.0000351 AC: 51 AN: 1453968 Hom.: 1 Cov.: 32 AF XY: 0.0000263 AC XY: 19 AN XY: 723596

African (AFR) AF: 0.00 AC: 0 AN: 33466

American (AMR) AF: 0.00 AC: 0 AN: 44682

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26058

East Asian (EAS) AF: 0.00 AC: 0 AN: 39692

South Asian (SAS) AF: 0.00 AC: 0 AN: 86146

European-Finnish (FIN) AF: 0.000151 AC: 7 AN: 46444

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5594

European-Non Finnish (NFE) AF: 0.0000333 AC: 37 AN: 1111608

Other (OTH) AF: 0.000116 AC: 7 AN: 60278

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.31
CADD	Benign	9.9
DANN	Benign	0.84
PhyloP100		0.76

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs768276521; hg19: chr19-5914969; COSMIC: COSV99222442; COSMIC: COSV99222442;