chr7-5527651-C-CA

Variant names:

• chr7-5527651-C-CA
• rs372205322
• NM_001101.5:c.*96dupT

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_001101.5(ACTB):​c.*96dupT 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
• 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: Benign. The variant received -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 VariationId 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 the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High AC in GnomAd4 at 4391 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.*96dupT		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.*96dupT		3_prime_UTR	Exon 6 of 6	ENSP00000494750.1	P60709
	ACTB	ENST00000425660.5	TSL:1	n.*887dupT		non_coding_transcript_exon	Exon 7 of 7	ENSP00000409264.1	G5E9R0
	ACTB	ENST00000425660.5	TSL:1	n.*887dupT		3_prime_UTR	Exon 7 of 7	ENSP00000409264.1	G5E9R0

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

African (AFR) AF: 0.0384 AC: 1004 AN: 26140

American (AMR) AF: 0.0212 AC: 676 AN: 31900

Ashkenazi Jewish (ASJ) AF: 0.0662 AC: 1418 AN: 21432

East Asian (EAS) AF: 0.0147 AC: 519 AN: 35242

South Asian (SAS) AF: 0.0333 AC: 2296 AN: 68892

European-Finnish (FIN) AF: 0.0145 AC: 626 AN: 43042

Middle Eastern (MID) AF: 0.0463 AC: 159 AN: 3432

European-Non Finnish (NFE) AF: 0.0384 AC: 34589 AN: 900768

Other (OTH) AF: 0.0353 AC: 1757 AN: 49720

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

African (AFR) AF: 0.0307 AC: 1213 AN: 39462

American (AMR) AF: 0.0278 AC: 407 AN: 14648

Ashkenazi Jewish (ASJ) AF: 0.0601 AC: 204 AN: 3392

East Asian (EAS) AF: 0.0118 AC: 58 AN: 4936

South Asian (SAS) AF: 0.0240 AC: 110 AN: 4592

European-Finnish (FIN) AF: 0.0110 AC: 102 AN: 9308

Middle Eastern (MID) AF: 0.0679 AC: 19 AN: 280

European-Non Finnish (NFE) AF: 0.0328 AC: 2161 AN: 65922

Other (OTH) AF: 0.0341 AC: 69 AN: 2024

Alfa AF: 0.00569 Hom.: 0

Asia WGS AF: 0.0230 AC: 81 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.027
Mutation Taster		=100/0	polymorphism

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;