chr19-36146703-A-G

Variant names:

• chr19-36146703-A-G
• rs17882574
• NM_001749.4:c.721+391A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001749.4(CAPNS1):​c.721+391A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0971 in 152,206 control chromosomes in the GnomAD database, including 806 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 0.097 (806 hom., cov: 32)
• Consequence: CAPNS1 NM_001749.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.63
• Publications: 1 publications found

Genes affected

CAPNS1 (HGNC:1481): (calpain small subunit 1) This gene is a member of the calpain small subunit family. Calpains are calcium-dependent cysteine proteinases that are widely distributed in mammalian cells. Calpains operate as heterodimers, comprising a specific large catalytic subunit (calpain 1 subunit in Calpain I, and calpain 2 subunit in Calpain II), and a common small regulatory subunit encoded by this gene. This encoded protein is essential for the stability and function of both calpain heterodimers, whose proteolytic activities influence various cellular functions including apoptosis, proliferation, migration, adhesion, and autophagy. Calpains have been implicated in neurodegenerative processes, such as myotonic dystrophy. A pseudogene of this gene has been defined on chromosome 1. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2014]

ENSG00000270760 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.11 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001749.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CAPNS1	NM_001749.4	MANE Select	c.721+391A>G		intron	N/A	NP_001740.1
	CAPNS1	NM_001003962.3		c.721+391A>G		intron	N/A	NP_001003962.1
	CAPNS1	NM_001302632.2		c.721+391A>G		intron	N/A	NP_001289561.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CAPNS1	ENST00000246533.8	TSL:1 MANE Select	c.721+391A>G		intron	N/A	ENSP00000246533.2
	CAPNS1	ENST00000587718.5	TSL:1	c.721+391A>G		intron	N/A	ENSP00000468041.1
	CAPNS1	ENST00000588815.5	TSL:1	c.721+391A>G		intron	N/A	ENSP00000464849.1

Frequencies

GnomAD3 genomes AF: 0.0971 AC: 14775 AN: 152088 Hom.: 805 Cov.: 32

Gnomad AFR AF: 0.113

Gnomad AMI AF: 0.110

Gnomad AMR AF: 0.0733

Gnomad ASJ AF: 0.0524

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0102

Gnomad FIN AF: 0.114

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.107

Gnomad OTH AF: 0.0937

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

GnomAD4 genome AF: 0.0971 AC: 14776 AN: 152206 Hom.: 806 Cov.: 32 AF XY: 0.0950 AC XY: 7069 AN XY: 74408

African (AFR) AF: 0.112 AC: 4665 AN: 41510

American (AMR) AF: 0.0731 AC: 1118 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0524 AC: 182 AN: 3470

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5180

South Asian (SAS) AF: 0.00975 AC: 47 AN: 4822

European-Finnish (FIN) AF: 0.114 AC: 1205 AN: 10606

Middle Eastern (MID) AF: 0.0306 AC: 9 AN: 294

European-Non Finnish (NFE) AF: 0.107 AC: 7252 AN: 68012

Other (OTH) AF: 0.0927 AC: 196 AN: 2114

Alfa AF: 0.0968 Hom.: 359

Bravo AF: 0.0943

Asia WGS AF: 0.0150 AC: 53 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	14
DANN	Benign	0.93
PhyloP100		1.6
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs17882574; hg19: chr19-36637605;