7-5527623-C-CA

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001101.5(ACTB):c.*124_*125insT variant causes a 3 prime UTR change. The variant allele was found at a frequency of 0.0774 in 59,234 control chromosomes in the GnomAD database, including 85 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.077 (85 hom., cov: 30)
  • Exomes 𝑓: 0.27 (23 hom.)
  • Failed GnomAD Quality Control
• Consequence: ACTB NM_001101.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 4.48

Genes affected

ACTB (HGNC:132): (actin beta) This gene encodes one of six different actin proteins. Actins are highly conserved proteins that are involved in cell motility, structure, integrity, and intercellular signaling. The encoded protein is a major constituent of the contractile apparatus and one of the two nonmuscle cytoskeletal actins that are ubiquitously expressed. Mutations in this gene cause Baraitser-Winter syndrome 1, which is characterized by intellectual disability with a distinctive facial appearance in human patients. Numerous pseudogenes of this gene have been identified throughout the human genome. [provided by RefSeq, Aug 2017]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 7-5527623-C-CA is Benign according to our data. Variant chr7-5527623-C-CA is described in ClinVar as [Benign]. Clinvar id is 1245930.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0931 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ACTB	NM_001101.5	c.*124_*125insT		3_prime_UTR_variant	6/6	ENST00000646664.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ACTB	ENST00000646664.1	c.*124_*125insT		3_prime_UTR_variant	6/6		NM_001101.5	P1

Frequencies

GnomAD3 genomes AF: 0.0773 AC: 4579 AN: 59202 Hom.: 84 Cov.: 30

Gnomad AFR AF: 0.0780

Gnomad AMI AF: 0.0747

Gnomad AMR AF: 0.0511

Gnomad ASJ AF: 0.0671

Gnomad EAS AF: 0.0450

Gnomad SAS AF: 0.103

Gnomad FIN AF: 0.0578

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.0846

Gnomad OTH AF: 0.0786

GnomAD4 exome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.267 AC: 279851 AN: 1048332 Hom.: 23 Cov.: 0 AF XY: 0.267 AC XY: 139949 AN XY: 524972

Gnomad4 AFR exome AF: 0.277

Gnomad4 AMR exome AF: 0.225

Gnomad4 ASJ exome AF: 0.259

Gnomad4 EAS exome AF: 0.268

Gnomad4 SAS exome AF: 0.272

Gnomad4 FIN exome AF: 0.223

Gnomad4 NFE exome AF: 0.270

Gnomad4 OTH exome AF: 0.269

GnomAD4 genome AF: 0.0774 AC: 4587 AN: 59234 Hom.: 85 Cov.: 30 AF XY: 0.0773 AC XY: 2188 AN XY: 28322

Gnomad4 AFR AF: 0.0782

Gnomad4 AMR AF: 0.0510

Gnomad4 ASJ AF: 0.0671

Gnomad4 EAS AF: 0.0455

Gnomad4 SAS AF: 0.105

Gnomad4 FIN AF: 0.0578

Gnomad4 NFE AF: 0.0846

Gnomad4 OTH AF: 0.0779

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

Aug 10, 2019

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Computational scores

Source: dbNSFP v4.3

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: rs370106412; hg19: chr7-5567254;