chr19-5914738-C-A

Variant names:

• chr19-5914738-C-A
• rs778058706
• NM_004058.5:c.259C>A

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_004058.5(CAPS):​c.259C>A​(p.Arg87Arg) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000055 in 1,453,438 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000055 (0 hom.)
• Consequence: CAPS NM_004058.5 splice_region, synonymous
• Scores: Splicing: ADA: 0.0003222
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.434
• 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 -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.51).
• BP7: Synonymous conserved (PhyloP=0.434 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.259C>A	p.Arg87Arg	splice_region synonymous	Exon 3 of 5	NP_004049.3	Q13938-4
	CAPS	NM_080590.4		c.259C>A	p.Arg87Arg	splice_region synonymous	Exon 3 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.259C>A	p.Arg87Arg	splice_region synonymous	Exon 3 of 5	ENSP00000465883.2	Q13938-4
	CAPS	ENST00000585541.1	TSL:1	n.392C>A		non_coding_transcript_exon	Exon 2 of 2
	CAPS	ENST00000961097.1		c.259C>A	p.Arg87Arg	splice_region synonymous	Exon 3 of 5	ENSP00000631156.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.0000124 AC: 3 AN: 242118 AF XY: 0.0000153

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000545

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000184

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000550 AC: 8 AN: 1453438 Hom.: 0 Cov.: 33 AF XY: 0.00000277 AC XY: 2 AN XY: 722306

African (AFR) AF: 0.00 AC: 0 AN: 33402

American (AMR) AF: 0.00 AC: 0 AN: 44254

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25392

East Asian (EAS) AF: 0.000151 AC: 6 AN: 39622

South Asian (SAS) AF: 0.00 AC: 0 AN: 84928

European-Finnish (FIN) AF: 0.0000190 AC: 1 AN: 52562

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5496

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1107742

Other (OTH) AF: 0.0000167 AC: 1 AN: 60040

GnomAD4 genome Cov.: 33

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
CADD	Benign	9.0
DANN	Benign	0.74
PhyloP100		0.43
PromoterAI		-0.014	Neutral

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00032
dbscSNV1_RF	Benign	0.028
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: rs778058706; hg19: chr19-5914749;