7-5527481-C-T

Position:

• chr7-5527481-C-T

Variant summary

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

The NM_001101.5(ACTB):​c.*267G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.352 in 551,678 control chromosomes in the GnomAD database, including 35,029 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.37 (10148 hom., cov: 30)
  • Exomes 𝑓: 0.35 (24881 hom.)
• Consequence: ACTB NM_001101.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.186

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.51).
• BP6: Variant 7-5527481-C-T is Benign according to our data. Variant chr7-5527481-C-T is described in ClinVar as [Benign]. Clinvar id is 1260131.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.395 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ACTB	NM_001101.5	c.*267G>A		3_prime_UTR_variant	6/6	ENST00000646664.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ACTB	ENST00000646664.1	c.*267G>A		3_prime_UTR_variant	6/6		NM_001101.5	P1

Frequencies

GnomAD3 genomes AF: 0.365 AC: 55279 AN: 151410 Hom.: 10142 Cov.: 30

Gnomad AFR AF: 0.401

Gnomad AMI AF: 0.274

Gnomad AMR AF: 0.349

Gnomad ASJ AF: 0.446

Gnomad EAS AF: 0.229

Gnomad SAS AF: 0.300

Gnomad FIN AF: 0.388

Gnomad MID AF: 0.379

Gnomad NFE AF: 0.356

Gnomad OTH AF: 0.367

GnomAD4 exome AF: 0.347 AC: 138768 AN: 400150 Hom.: 24881 Cov.: 5 AF XY: 0.345 AC XY: 73294 AN XY: 212264

Gnomad4 AFR exome AF: 0.402

Gnomad4 AMR exome AF: 0.353

Gnomad4 ASJ exome AF: 0.439

Gnomad4 EAS exome AF: 0.229

Gnomad4 SAS exome AF: 0.310

Gnomad4 FIN exome AF: 0.391

Gnomad4 NFE exome AF: 0.353

Gnomad4 OTH exome AF: 0.352

GnomAD4 genome AF: 0.365 AC: 55324 AN: 151528 Hom.: 10148 Cov.: 30 AF XY: 0.365 AC XY: 26973 AN XY: 73968

Gnomad4 AFR AF: 0.401

Gnomad4 AMR AF: 0.349

Gnomad4 ASJ AF: 0.446

Gnomad4 EAS AF: 0.230

Gnomad4 SAS AF: 0.302

Gnomad4 FIN AF: 0.388

Gnomad4 NFE AF: 0.356

Gnomad4 OTH AF: 0.364

Alfa AF: 0.352 Hom.: 1275

Bravo AF: 0.367

Asia WGS AF: 0.303 AC: 1052 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

Aug 15, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
CADD	Benign	11
DANN	Benign	0.86
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: rs7612; hg19: chr7-5567112; COSMIC: COSV59319102; COSMIC: COSV59319102;