7-5527651-C-CA

Position:

• chr7-5527651-C-CA

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_001101.5(ACTB):​c.*96_*97insT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0302 in 145,440 control chromosomes in the GnomAD database, including 70 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.030 (70 hom., cov: 31)
  • Exomes 𝑓: 0.036 (748 hom.)
  • Failed GnomAD Quality Control
• Consequence: ACTB NM_001101.5 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0270

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 7-5527651-C-CA is Benign according to our data. Variant chr7-5527651-C-CA is described in ClinVar as [Likely_benign]. Clinvar id is 1213113.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0302 (4391/145440) while in subpopulation NFE AF= 0.0328 (2161/65922). AF 95% confidence interval is 0.0316. There are 70 homozygotes in gnomad4. There are 2017 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 4391 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ACTB	NM_001101.5	c.*96_*97insT		3_prime_UTR_variant	6/6	ENST00000646664.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ACTB	ENST00000646664.1	c.*96_*97insT		3_prime_UTR_variant	6/6		NM_001101.5	P1

Frequencies

GnomAD3 genomes AF: 0.0302 AC: 4389 AN: 145374 Hom.: 70 Cov.: 31

Gnomad AFR AF: 0.0307

Gnomad AMI AF: 0.0548

Gnomad AMR AF: 0.0278

Gnomad ASJ AF: 0.0601

Gnomad EAS AF: 0.0117

Gnomad SAS AF: 0.0241

Gnomad FIN AF: 0.0110

Gnomad MID AF: 0.0691

Gnomad NFE AF: 0.0328

Gnomad OTH AF: 0.0343

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0365 AC: 43044 AN: 1180568 Hom.: 748 Cov.: 30 AF XY: 0.0362 AC XY: 21358 AN XY: 589430

Gnomad4 AFR exome AF: 0.0384

Gnomad4 AMR exome AF: 0.0212

Gnomad4 ASJ exome AF: 0.0662

Gnomad4 EAS exome AF: 0.0147

Gnomad4 SAS exome AF: 0.0333

Gnomad4 FIN exome AF: 0.0145

Gnomad4 NFE exome AF: 0.0384

Gnomad4 OTH exome AF: 0.0353

GnomAD4 genome AF: 0.0302 AC: 4391 AN: 145440 Hom.: 70 Cov.: 31 AF XY: 0.0285 AC XY: 2017 AN XY: 70664

Gnomad4 AFR AF: 0.0307

Gnomad4 AMR AF: 0.0278

Gnomad4 ASJ AF: 0.0601

Gnomad4 EAS AF: 0.0118

Gnomad4 SAS AF: 0.0240

Gnomad4 FIN AF: 0.0110

Gnomad4 NFE AF: 0.0328

Gnomad4 OTH AF: 0.0341

Asia WGS AF: 0.0230 AC: 81 AN: 3478

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

Aug 06, 2019

- -

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: rs372205322; hg19: chr7-5567282;