17-81510463-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001614.5(ACTG1):c.*227C>T variant causes a 3 prime UTR change. The variant allele was found at a frequency of 0.00177 in 693,992 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0024 (4 hom., cov: 32)
  • Exomes 𝑓: 0.0016 (3 hom.)
• Consequence: ACTG1 NM_001614.5 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 4.79

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=-0.47).
• BP6: Variant 17-81510463-G-A is Benign according to our data. Variant chr17-81510463-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1195787.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00239 (364/152200) while in subpopulation AMR AF= 0.00144 (22/15290). AF 95% confidence interval is 0.00116. There are 4 homozygotes in gnomad4. There are 246 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd at 364 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ACTG1	NM_001614.5	c.*227C>T		3_prime_UTR_variant	6/6	ENST00000573283.7
ACTG1	NM_001199954.3	c.*227C>T		3_prime_UTR_variant	6/6
ACTG1	NR_037688.3	n.1411+16C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ACTG1	ENST00000573283.7	c.*227C>T		3_prime_UTR_variant	6/6	5	NM_001614.5	P4

Frequencies

GnomAD3 genomes AF: 0.00239 AC: 364 AN: 152082 Hom.: 4 Cov.: 32

Gnomad AFR AF: 0.000435

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00144

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0217

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00138

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.00137 AC: 189 AN: 137458 Hom.: 2 AF XY: 0.00118 AC XY: 88 AN XY: 74528

Gnomad AFR exome AF: 0.000299

Gnomad AMR exome AF: 0.000735

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.0175

Gnomad NFE exome AF: 0.00106

Gnomad OTH exome AF: 0.00217

GnomAD4 exome AF: 0.00159 AC: 864 AN: 541792 Hom.: 3 Cov.: 6 AF XY: 0.00141 AC XY: 413 AN XY: 292264

Gnomad4 AFR exome AF: 0.000259

Gnomad4 AMR exome AF: 0.000774

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000323

Gnomad4 FIN exome AF: 0.0146

Gnomad4 NFE exome AF: 0.00107

Gnomad4 OTH exome AF: 0.00129

GnomAD4 genome AF: 0.00239 AC: 364 AN: 152200 Hom.: 4 Cov.: 32 AF XY: 0.00331 AC XY: 246 AN XY: 74410

Gnomad4 AFR AF: 0.000434

Gnomad4 AMR AF: 0.00144

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.0217

Gnomad4 NFE AF: 0.00138

Gnomad4 OTH AF: 0.00

Alfa AF: 0.00101 Hom.: 0

Bravo AF: 0.000937

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 15, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
Cadd	Benign	18
Dann	Benign	0.90
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: rs184661152; hg19: chr17-79477489;