19-38731075-CCCATGCCCCA-C

Position:

• chr19-38731075-CCCATGCCCCA-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_004924.6(ACTN4):​c.*1651_*1660delCCACCATGCC variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.173 in 1,587,832 control chromosomes in the GnomAD database, including 25,083 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.15 (2053 hom., cov: 29)
  • Exomes 𝑓: 0.17 (23030 hom.)
• Consequence: ACTN4 NM_004924.6 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.154

Genes affected

ACTN4 (HGNC:166): (actinin alpha 4) Alpha actinins belong to the spectrin gene superfamily which represents a diverse group of cytoskeletal proteins, including the alpha and beta spectrins and dystrophins. Alpha actinin is an actin-binding protein with multiple roles in different cell types. In nonmuscle cells, the cytoskeletal isoform is found along microfilament bundles and adherens-type junctions, where it is involved in binding actin to the membrane. In contrast, skeletal, cardiac, and smooth muscle isoforms are localized to the Z-disc and analogous dense bodies, where they help anchor the myofibrillar actin filaments. This gene encodes a nonmuscle, alpha actinin isoform which is concentrated in the cytoplasm, and thought to be involved in metastatic processes. Mutations in this gene have been associated with focal and segmental glomerulosclerosis. [provided by RefSeq, Jul 2008]

CAPN12 (HGNC:13249): (calpain 12) The calpains, calcium-activated neutral proteases, are nonlysosomal, intracellular cysteine proteases. The mammalian calpains include ubiquitous, stomach-specific, and muscle-specific proteins. The ubiquitous enzymes consist of heterodimers with distinct large, catalytic subunits associated with a common small, regulatory subunit. This gene encodes a member of the calpain large subunit family. [provided by RefSeq, Jun 2012]

CAPN12 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 19-38731075-CCCATGCCCCA-C is Benign according to our data. Variant chr19-38731075-CCCATGCCCCA-C is described in ClinVar as [Benign]. Clinvar id is 1293786.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.19 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ACTN4	NM_004924.6	c.*1651_*1660delCCACCATGCC		3_prime_UTR_variant	21/21	ENST00000252699.7	NP_004915.2
CAPN12	NM_144691.4	c.2074+22_2074+31delTGGGGCATGG		intron_variant		ENST00000328867.9	NP_653292.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ACTN4	ENST00000252699.7	c.*1651_*1660delCCACCATGCC		3_prime_UTR_variant	21/21	1	NM_004924.6	ENSP00000252699.2
CAPN12	ENST00000328867.9	c.2074+22_2074+31delTGGGGCATGG		intron_variant		1	NM_144691.4	ENSP00000331636.3

Frequencies

GnomAD3 genomes AF: 0.153 AC: 23196 AN: 151948 Hom.: 2052 Cov.: 29

Gnomad AFR AF: 0.0863

Gnomad AMI AF: 0.348

Gnomad AMR AF: 0.161

Gnomad ASJ AF: 0.217

Gnomad EAS AF: 0.00829

Gnomad SAS AF: 0.159

Gnomad FIN AF: 0.160

Gnomad MID AF: 0.334

Gnomad NFE AF: 0.193

Gnomad OTH AF: 0.187

GnomAD3 exomes AF: 0.174 AC: 35906 AN: 206704 Hom.: 3260 AF XY: 0.180 AC XY: 20224 AN XY: 112242

Gnomad AFR exome AF: 0.0994

Gnomad AMR exome AF: 0.115

Gnomad ASJ exome AF: 0.225

Gnomad EAS exome AF: 0.00418

Gnomad SAS exome AF: 0.172

Gnomad FIN exome AF: 0.177

Gnomad NFE exome AF: 0.225

Gnomad OTH exome AF: 0.208

GnomAD4 exome AF: 0.175 AC: 251212 AN: 1435766 Hom.: 23030 AF XY: 0.177 AC XY: 125869 AN XY: 712110

Gnomad4 AFR exome AF: 0.0877

Gnomad4 AMR exome AF: 0.120

Gnomad4 ASJ exome AF: 0.219

Gnomad4 EAS exome AF: 0.00233

Gnomad4 SAS exome AF: 0.167

Gnomad4 FIN exome AF: 0.168

Gnomad4 NFE exome AF: 0.185

Gnomad4 OTH exome AF: 0.170

GnomAD4 genome AF: 0.153 AC: 23205 AN: 152066 Hom.: 2053 Cov.: 29 AF XY: 0.151 AC XY: 11233 AN XY: 74334

Gnomad4 AFR AF: 0.0863

Gnomad4 AMR AF: 0.161

Gnomad4 ASJ AF: 0.217

Gnomad4 EAS AF: 0.00830

Gnomad4 SAS AF: 0.158

Gnomad4 FIN AF: 0.160

Gnomad4 NFE AF: 0.193

Gnomad4 OTH AF: 0.186

Alfa AF: 0.180 Hom.: 429

Bravo AF: 0.149

Asia WGS AF: 0.0830 AC: 288 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 09, 2018

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs141208726; hg19: chr19-39221715;