7-5527481-C-T

Variant names:

• chr7-5527481-C-T
• rs7612
• NM_001101.5:c.*267G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001101.5(ACTB):​c.*267G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.352 in 551,678 control chromosomes in the GnomAD database, including 35,029 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.37 (10148 hom., cov: 30)
  • Exomes 𝑓: 0.35 (24881 hom.)
• Consequence: ACTB NM_001101.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.186
• Publications: 13 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.51).
• BP6: Variant 7-5527481-C-T is Benign according to our data. Variant chr7-5527481-C-T is described in ClinVar as Benign. ClinVar VariationId is 1260131.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.395 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.*267G>A		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.*267G>A		3_prime_UTR	Exon 6 of 6	ENSP00000494750.1	P60709
	ACTB	ENST00000425660.5	TSL:1	n.*1058G>A		non_coding_transcript_exon	Exon 7 of 7	ENSP00000409264.1	G5E9R0
	ACTB	ENST00000425660.5	TSL:1	n.*1058G>A		3_prime_UTR	Exon 7 of 7	ENSP00000409264.1	G5E9R0

Frequencies

GnomAD3 genomes AF: 0.365 AC: 55279 AN: 151410 Hom.: 10142 Cov.: 30

Gnomad AFR AF: 0.401

Gnomad AMI AF: 0.274

Gnomad AMR AF: 0.349

Gnomad ASJ AF: 0.446

Gnomad EAS AF: 0.229

Gnomad SAS AF: 0.300

Gnomad FIN AF: 0.388

Gnomad MID AF: 0.379

Gnomad NFE AF: 0.356

Gnomad OTH AF: 0.367

GnomAD4 exome AF: 0.347 AC: 138768 AN: 400150 Hom.: 24881 Cov.: 5 AF XY: 0.345 AC XY: 73294 AN XY: 212264

African (AFR) AF: 0.402 AC: 4482 AN: 11136

American (AMR) AF: 0.353 AC: 5631 AN: 15946

Ashkenazi Jewish (ASJ) AF: 0.439 AC: 4993 AN: 11370

East Asian (EAS) AF: 0.229 AC: 5385 AN: 23552

South Asian (SAS) AF: 0.310 AC: 13575 AN: 43854

European-Finnish (FIN) AF: 0.391 AC: 8470 AN: 21674

Middle Eastern (MID) AF: 0.366 AC: 601 AN: 1642

European-Non Finnish (NFE) AF: 0.353 AC: 87906 AN: 249000

Other (OTH) AF: 0.352 AC: 7725 AN: 21976

GnomAD4 genome AF: 0.365 AC: 55324 AN: 151528 Hom.: 10148 Cov.: 30 AF XY: 0.365 AC XY: 26973 AN XY: 73968

African (AFR) AF: 0.401 AC: 16544 AN: 41298

American (AMR) AF: 0.349 AC: 5308 AN: 15216

Ashkenazi Jewish (ASJ) AF: 0.446 AC: 1547 AN: 3472

East Asian (EAS) AF: 0.230 AC: 1184 AN: 5152

South Asian (SAS) AF: 0.302 AC: 1446 AN: 4794

European-Finnish (FIN) AF: 0.388 AC: 4046 AN: 10434

Middle Eastern (MID) AF: 0.377 AC: 110 AN: 292

European-Non Finnish (NFE) AF: 0.356 AC: 24125 AN: 67856

Other (OTH) AF: 0.364 AC: 765 AN: 2104

Alfa AF: 0.354 Hom.: 1732

Bravo AF: 0.367

Asia WGS AF: 0.303 AC: 1052 AN: 3478

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
BayesDel_noAF	Benign	-0.51
CADD	Benign	11
DANN	Benign	0.86
PhyloP100		0.19
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs7612; hg19: chr7-5567112; COSMIC: COSV59319102; COSMIC: COSV59319102;