Variant 17-81510578-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001614.5(ACTG1):c.*112C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00236 in 1,378,522 control chromosomes in the GnomAD database, including 70 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0012 ( 5 hom., cov: 32)

Exomes 𝑓: 0.0025 ( 65 hom. )

Consequence

ACTG1
NM_001614.5 3_prime_UTR

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.332

Variant links:

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]

ACTG1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.5).

BP6

Variant 17-81510578-G-A is Benign according to our data. Variant chr17-81510578-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1198354.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00122 (186/152324) while in subpopulation SAS AF= 0.0329 (159/4830). AF 95% confidence interval is 0.0287. There are 5 homozygotes in gnomad4. There are 132 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 186 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE
ACTG1	NM_001614.5 linkuse as main transcript	c.*112C>T	3_prime_UTR_variant	6/6	ENST00000573283.7
ACTG1	NM_001199954.3 linkuse as main transcript	c.*112C>T	3_prime_UTR_variant	6/6
ACTG1	NR_037688.3 linkuse as main transcript	n.1312C>T	non_coding_transcript_exon_variant	6/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ACTG1	ENST00000573283.7 linkuse as main transcript	c.*112C>T		3_prime_UTR_variant	6/6	5	NM_001614.5	P4

Frequencies

GnomAD3 genomes

AF:

0.00122

AC:

186

AN:

152206

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00173

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0329

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000176

Gnomad OTH

AF:

0.000957

GnomAD3 exomes

AF:

0.00400

AC:

942

AN:

235458

Hom.:

AF XY:

0.00542

AC XY:

697

AN XY:

128700

show subpopulations

Gnomad AFR exome

AF:

0.000146

Gnomad AMR exome

AF:

0.000181

Gnomad ASJ exome

AF:

0.00247

Gnomad EAS exome

AF:

0.000459

Gnomad SAS exome

AF:

0.0279

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000487

Gnomad OTH exome

AF:

0.00275

GnomAD4 exome

AF:

0.00250

AC:

3068

AN:

1226198

Hom.:

Cov.:

AF XY:

0.00349

AC XY:

2164

AN XY:

620856

show subpopulations

Gnomad4 AFR exome

AF:

0.000175

Gnomad4 AMR exome

AF:

0.000162

Gnomad4 ASJ exome

AF:

0.00308

Gnomad4 EAS exome

AF:

0.000130

Gnomad4 SAS exome

AF:

0.0300

Gnomad4 FIN exome

AF:

0.0000192

Gnomad4 NFE exome

AF:

0.000408

Gnomad4 OTH exome

AF:

0.00273

GnomAD4 genome

AF:

0.00122

AC:

186

AN:

152324

Hom.:

Cov.:

AF XY:

0.00177

AC XY:

132

AN XY:

74490

show subpopulations

Gnomad4 AFR

AF:

0.000120

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00173

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0329

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000176

Gnomad4 OTH

AF:

0.000947

Alfa

AF:

0.000983

Hom.:

Bravo

AF:

0.000404

Asia WGS

AF:

0.00606

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 28, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.50

CADD

Benign

8.0

DANN

Benign

0.91

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over