7-5527651-CAAAAA-CAA

Variant names:

• chr7-5527651-CAAA-C
• rs372205322
• NM_001101.5:c.*94_*96delTTT

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_001101.5(ACTB):​c.*94_*96delTTT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000413 in 145,404 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000041 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000047 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ACTB NM_001101.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.324
• Publications: 0 publications found

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]

ACTB Gene-Disease associations (from GenCC):

• Baraitser-Winter cerebrofrontofacial syndrome

  Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, ClinGen
• Baraitser-Winter syndrome 1

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, Genomics England PanelApp, Labcorp Genetics (formerly Invitae), PanelApp Australia
• developmental malformations-deafness-dystonia syndrome

  Inheritance: AD Classification: STRONG, SUPPORTIVE, LIMITED Submitted by: Orphanet, Genomics England PanelApp, Labcorp Genetics (formerly Invitae), Illumina, PanelApp Australia
• ACTB-associated syndromic thrombocytopenia

  Inheritance: AD Classification: MODERATE Submitted by: ClinGen, Ambry Genetics

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BS2: High AC in GnomAd4 at 6 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001101.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACTB	NM_001101.5	MANE Select	c.*94_*96delTTT		3_prime_UTR	Exon 6 of 6	NP_001092.1	P60709

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACTB	ENST00000646664.1	MANE Select	c.*94_*96delTTT		3_prime_UTR	Exon 6 of 6	ENSP00000494750.1	P60709
	ACTB	ENST00000425660.5	TSL:1	n.*885_*887delTTT		non_coding_transcript_exon	Exon 7 of 7	ENSP00000409264.1	G5E9R0
	ACTB	ENST00000425660.5	TSL:1	n.*885_*887delTTT		3_prime_UTR	Exon 7 of 7	ENSP00000409264.1	G5E9R0

Frequencies

GnomAD3 genomes AF: 0.0000413 AC: 6 AN: 145404 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000254

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000758

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000466 AC: 55 AN: 1181218 Hom.: 0 AF XY: 0.0000543 AC XY: 32 AN XY: 589762

African (AFR) AF: 0.00 AC: 0 AN: 26168

American (AMR) AF: 0.00 AC: 0 AN: 31916

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21446

East Asian (EAS) AF: 0.00 AC: 0 AN: 35254

South Asian (SAS) AF: 0.00 AC: 0 AN: 68934

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 43052

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3438

European-Non Finnish (NFE) AF: 0.0000544 AC: 49 AN: 901264

Other (OTH) AF: 0.000121 AC: 6 AN: 49746

GnomAD4 genome AF: 0.0000413 AC: 6 AN: 145404 Hom.: 0 Cov.: 31 AF XY: 0.0000425 AC XY: 3 AN XY: 70588

African (AFR) AF: 0.0000254 AC: 1 AN: 39382

American (AMR) AF: 0.00 AC: 0 AN: 14634

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3392

East Asian (EAS) AF: 0.00 AC: 0 AN: 4944

South Asian (SAS) AF: 0.00 AC: 0 AN: 4604

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9308

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 304

European-Non Finnish (NFE) AF: 0.0000758 AC: 5 AN: 65948

Other (OTH) AF: 0.00 AC: 0 AN: 2012

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.32

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

Other links and lift over

dbSNP: rs372205322; hg19: chr7-5567282;