chr7-5527623-CA-C

Variant names:

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

Variant summary

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

The NM_001101.5(ACTB):​c.*124delT variant causes a 3 prime UTR change. The variant allele was found at a frequency of 0.133 in 1,134,546 control chromosomes in the GnomAD database, including 104 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.080 (77 hom., cov: 30)
  • Exomes 𝑓: 0.14 (27 hom.)
• 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-CA-C is Benign according to our data. Variant chr7-5527623-CA-C is described in ClinVar as Benign. ClinVar VariationId is 1272390.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.101 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.*124delT		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.*124delT		3_prime_UTR	Exon 6 of 6	ENSP00000494750.1	P60709
	ACTB	ENST00000425660.5	TSL:1	n.*915delT		non_coding_transcript_exon	Exon 7 of 7	ENSP00000409264.1	G5E9R0
	ACTB	ENST00000425660.5	TSL:1	n.*915delT		3_prime_UTR	Exon 7 of 7	ENSP00000409264.1	G5E9R0

Frequencies

GnomAD3 genomes AF: 0.0801 AC: 4791 AN: 59812 Hom.: 77 Cov.: 30

Gnomad AFR AF: 0.0523

Gnomad AMI AF: 0.0537

Gnomad AMR AF: 0.0642

Gnomad ASJ AF: 0.0699

Gnomad EAS AF: 0.00668

Gnomad SAS AF: 0.0264

Gnomad FIN AF: 0.0950

Gnomad MID AF: 0.0500

Gnomad NFE AF: 0.104

Gnomad OTH AF: 0.0829

GnomAD4 exome AF: 0.136 AC: 145887 AN: 1074702 Hom.: 27 Cov.: 0 AF XY: 0.136 AC XY: 73275 AN XY: 538540

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

African (AFR) AF: 0.119 AC: 2863 AN: 23962

American (AMR) AF: 0.157 AC: 4456 AN: 28374

Ashkenazi Jewish (ASJ) AF: 0.136 AC: 2662 AN: 19630

East Asian (EAS) AF: 0.132 AC: 4364 AN: 33110

South Asian (SAS) AF: 0.117 AC: 7441 AN: 63744

European-Finnish (FIN) AF: 0.163 AC: 6118 AN: 37648

Middle Eastern (MID) AF: 0.115 AC: 347 AN: 3016

European-Non Finnish (NFE) AF: 0.136 AC: 111617 AN: 819662

Other (OTH) AF: 0.132 AC: 6019 AN: 45556

⚠️ 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: 0.0801 AC: 4792 AN: 59844 Hom.: 77 Cov.: 30 AF XY: 0.0787 AC XY: 2251 AN XY: 28588

African (AFR) AF: 0.0523 AC: 786 AN: 15042

American (AMR) AF: 0.0640 AC: 361 AN: 5642

Ashkenazi Jewish (ASJ) AF: 0.0699 AC: 104 AN: 1488

East Asian (EAS) AF: 0.00674 AC: 12 AN: 1780

South Asian (SAS) AF: 0.0270 AC: 50 AN: 1852

European-Finnish (FIN) AF: 0.0950 AC: 296 AN: 3116

Middle Eastern (MID) AF: 0.0510 AC: 5 AN: 98

European-Non Finnish (NFE) AF: 0.104 AC: 3091 AN: 29644

Other (OTH) AF: 0.0821 AC: 68 AN: 828

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 (auto)

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;