17-81510406-T-C

Position:

• chr17-81510406-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001614.5(ACTG1):​c.*284A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0243 in 534,420 control chromosomes in the GnomAD database, including 361 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.040 (225 hom., cov: 32)
  • Exomes 𝑓: 0.018 (136 hom.)
• Consequence: ACTG1 NM_001614.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0950

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 17-81510406-T-C is Benign according to our data. Variant chr17-81510406-T-C is described in ClinVar as [Benign]. Clinvar id is 1272736.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 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.*284A>G		3_prime_UTR_variant	6/6	ENST00000573283.7
ACTG1	NM_001199954.3	c.*284A>G		3_prime_UTR_variant	6/6
ACTG1	NR_037688.3	n.1411+73A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ACTG1	ENST00000573283.7	c.*284A>G		3_prime_UTR_variant	6/6	5	NM_001614.5	P4

Frequencies

GnomAD3 genomes AF: 0.0403 AC: 6131 AN: 152182 Hom.: 227 Cov.: 32

Gnomad AFR AF: 0.101

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.0301

Gnomad ASJ AF: 0.0513

Gnomad EAS AF: 0.0331

Gnomad SAS AF: 0.0172

Gnomad FIN AF: 0.00555

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0135

Gnomad OTH AF: 0.0411

GnomAD4 exome AF: 0.0180 AC: 6861 AN: 382120 Hom.: 136 Cov.: 4 AF XY: 0.0174 AC XY: 3609 AN XY: 207994

Gnomad4 AFR exome AF: 0.0943

Gnomad4 AMR exome AF: 0.0203

Gnomad4 ASJ exome AF: 0.0464

Gnomad4 EAS exome AF: 0.0221

Gnomad4 SAS exome AF: 0.0161

Gnomad4 FIN exome AF: 0.00516

Gnomad4 NFE exome AF: 0.0127

Gnomad4 OTH exome AF: 0.0252

GnomAD4 genome AF: 0.0403 AC: 6140 AN: 152300 Hom.: 225 Cov.: 32 AF XY: 0.0399 AC XY: 2968 AN XY: 74464

Gnomad4 AFR AF: 0.101

Gnomad4 AMR AF: 0.0301

Gnomad4 ASJ AF: 0.0513

Gnomad4 EAS AF: 0.0330

Gnomad4 SAS AF: 0.0170

Gnomad4 FIN AF: 0.00555

Gnomad4 NFE AF: 0.0135

Gnomad4 OTH AF: 0.0411

Alfa AF: 0.0263 Hom.: 11

Bravo AF: 0.0439

Asia WGS AF: 0.0400 AC: 137 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 26, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	10
DANN	Benign	0.70
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: rs11549167; hg19: chr17-79477432;