chr19-38647923-GC-G

Variant names:

• chr19-38647923-GC-G
• rs1568666913
• NM_004924.6:c.162+18delC

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_004924.6(ACTN4):​c.162+18delC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000203 in 1,328,374 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.000020 (0 hom.)
• Consequence: ACTN4 NM_004924.6 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.904
• Publications: 0 publications found

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]

ACTN4 Gene-Disease associations (from GenCC):

• focal segmental glomerulosclerosis 1

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• familial idiopathic steroid-resistant nephrotic syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP6: Variant 19-38647923-GC-G is Benign according to our data. Variant chr19-38647923-GC-G is described in ClinVar as Likely_benign. ClinVar VariationId is 1144244.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAdExome4 at 27 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004924.6. 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
	ACTN4	NM_004924.6	MANE Select	c.162+18delC		intron	N/A	NP_004915.2
	ACTN4	NM_001440296.1		c.162+18delC		intron	N/A	NP_001427225.1
	ACTN4	NM_001440300.1		c.162+18delC		intron	N/A	NP_001427229.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACTN4	ENST00000252699.7	TSL:1 MANE Select	c.162+17delC		intron	N/A	ENSP00000252699.2	O43707-1
	ACTN4	ENST00000424234.7	TSL:1	c.162+17delC		intron	N/A	ENSP00000411187.4	F5GXS2
	ACTN4	ENST00000390009.7	TSL:1	c.162+17delC		intron	N/A	ENSP00000439497.1	O43707-2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.0000107 AC: 1 AN: 93260 AF XY: 0.0000195

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: 0.00

Gnomad NFE exome AF: 0.0000275

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000203 AC: 27 AN: 1328374 Hom.: 0 Cov.: 32 AF XY: 0.0000199 AC XY: 13 AN XY: 652448

African (AFR) AF: 0.00 AC: 0 AN: 27384

American (AMR) AF: 0.00 AC: 0 AN: 27080

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21576

East Asian (EAS) AF: 0.00 AC: 0 AN: 30852

South Asian (SAS) AF: 0.00 AC: 0 AN: 70634

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 45726

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4084

European-Non Finnish (NFE) AF: 0.0000258 AC: 27 AN: 1046404

Other (OTH) AF: 0.00 AC: 0 AN: 54634

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.90

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: rs1568666913; hg19: chr19-39138563;