17-81510498-C-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001614.5(ACTG1):c.*192G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.022 in 779,208 control chromosomes in the GnomAD database, including 426 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.040 (223 hom., cov: 32)
  • Exomes 𝑓: 0.018 (203 hom.)
• Consequence: ACTG1 NM_001614.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.80

Genes affected

ACTG1 (HGNC:144): (actin gamma 1) Actins are highly conserved proteins that are involved in various types of cell motility and in maintenance of the cytoskeleton. Three main groups of actin isoforms have been identified in vertebrate animals: alpha, beta, and gamma. The alpha actins are found in muscle tissues and are a major constituent of the contractile apparatus. The beta and gamma actins co-exist in most cell types as components of the cytoskeleton and as mediators of internal cell motility. Actin gamma 1, encoded by this gene, is a cytoplasmic actin found in all cell types. Mutations in this gene are associated with DFNA20/26, a subtype of autosomal dominant non-syndromic sensorineural progressive hearing loss and also with Baraitser-Winter syndrome. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2017]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.64).
• BP6: Variant 17-81510498-C-G is Benign according to our data. Variant chr17-81510498-C-G is described in ClinVar as [Benign]. Clinvar id is 1268147.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.098 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ACTG1	NM_001614.5	c.*192G>C		3_prime_UTR_variant	6/6	ENST00000573283.7
ACTG1	NM_001199954.3	c.*192G>C		3_prime_UTR_variant	6/6
ACTG1	NR_037688.3	n.1392G>C		non_coding_transcript_exon_variant	6/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ACTG1	ENST00000573283.7	c.*192G>C		3_prime_UTR_variant	6/6	5	NM_001614.5	P4

Frequencies

GnomAD3 genomes AF: 0.0403 AC: 6126 AN: 152170 Hom.: 225 Cov.: 32

Gnomad AFR AF: 0.101

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.0300

Gnomad ASJ AF: 0.0513

Gnomad EAS AF: 0.0331

Gnomad SAS AF: 0.0168

Gnomad FIN AF: 0.00556

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0135

Gnomad OTH AF: 0.0412

GnomAD3 exomes AF: 0.0223 AC: 3248 AN: 145614 Hom.: 71 AF XY: 0.0209 AC XY: 1649 AN XY: 78776

Gnomad AFR exome AF: 0.101

Gnomad AMR exome AF: 0.0205

Gnomad ASJ exome AF: 0.0479

Gnomad EAS exome AF: 0.0297

Gnomad SAS exome AF: 0.0163

Gnomad FIN exome AF: 0.00499

Gnomad NFE exome AF: 0.0137

Gnomad OTH exome AF: 0.0208

GnomAD4 exome AF: 0.0175 AC: 10975 AN: 626920 Hom.: 203 Cov.: 8 AF XY: 0.0169 AC XY: 5665 AN XY: 334630

Gnomad4 AFR exome AF: 0.0936

Gnomad4 AMR exome AF: 0.0206

Gnomad4 ASJ exome AF: 0.0491

Gnomad4 EAS exome AF: 0.0206

Gnomad4 SAS exome AF: 0.0166

Gnomad4 FIN exome AF: 0.00534

Gnomad4 NFE exome AF: 0.0127

Gnomad4 OTH exome AF: 0.0253

GnomAD4 genome AF: 0.0403 AC: 6135 AN: 152288 Hom.: 223 Cov.: 32 AF XY: 0.0399 AC XY: 2970 AN XY: 74476

Gnomad4 AFR AF: 0.101

Gnomad4 AMR AF: 0.0300

Gnomad4 ASJ AF: 0.0513

Gnomad4 EAS AF: 0.0329

Gnomad4 SAS AF: 0.0166

Gnomad4 FIN AF: 0.00556

Gnomad4 NFE AF: 0.0135

Gnomad4 OTH AF: 0.0412

Alfa AF: 0.0280 Hom.: 20

Bravo AF: 0.0439

Asia WGS AF: 0.0400 AC: 137 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

Jun 14, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
Cadd	Benign	16
Dann	Benign	0.77
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Publications

LitVar

Other links and lift over

dbSNP: rs3204704; hg19: chr17-79477524;