7-5527623-CAAAAA-CAAAAAA

Variant names:

• chr7-5527623-C-CA
• rs370106412
• NM_001101.5:c.*124dupT

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001101.5(ACTB):​c.*124dupT 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
• Publications: 1 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, Labcorp Genetics (formerly Invitae), Genomics England PanelApp
• developmental malformations-deafness-dystonia syndrome

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

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

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

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.*124dupT		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.*124dupT		3_prime_UTR	Exon 6 of 6	ENSP00000494750.1	P60709
	ACTB	ENST00000425660.5	TSL:1	n.*915dupT		non_coding_transcript_exon	Exon 7 of 7	ENSP00000409264.1	G5E9R0
	ACTB	ENST00000425660.5	TSL:1	n.*915dupT		3_prime_UTR	Exon 7 of 7	ENSP00000409264.1	G5E9R0

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

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.277 AC: 6463 AN: 23316

American (AMR) AF: 0.225 AC: 6226 AN: 27674

Ashkenazi Jewish (ASJ) AF: 0.259 AC: 4960 AN: 19120

East Asian (EAS) AF: 0.268 AC: 8695 AN: 32494

South Asian (SAS) AF: 0.272 AC: 16318 AN: 60078

European-Finnish (FIN) AF: 0.223 AC: 8349 AN: 37424

Middle Eastern (MID) AF: 0.295 AC: 868 AN: 2946

European-Non Finnish (NFE) AF: 0.270 AC: 216047 AN: 801006

Other (OTH) AF: 0.269 AC: 11925 AN: 44274

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

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

African (AFR) AF: 0.0782 AC: 1165 AN: 14896

American (AMR) AF: 0.0510 AC: 285 AN: 5588

Ashkenazi Jewish (ASJ) AF: 0.0671 AC: 98 AN: 1460

East Asian (EAS) AF: 0.0455 AC: 80 AN: 1760

South Asian (SAS) AF: 0.105 AC: 192 AN: 1824

European-Finnish (FIN) AF: 0.0578 AC: 180 AN: 3114

Middle Eastern (MID) AF: 0.163 AC: 16 AN: 98

European-Non Finnish (NFE) AF: 0.0846 AC: 2481 AN: 29324

Other (OTH) AF: 0.0779 AC: 64 AN: 822

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: 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		4.5
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: rs370106412; hg19: chr7-5567254;