chr7-5527488-C-T

Variant names:

• chr7-5527488-C-T
• rs11546906
• NM_001101.5:c.*260G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001101.5(ACTB):​c.*260G>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 0.00364 in 580,596 control chromosomes in the GnomAD database, including 44 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.010 (36 hom., cov: 29)
  • Exomes 𝑓: 0.0012 (8 hom.)
• Consequence: ACTB NM_001101.5 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.62
• 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).
• BP6: Variant 7-5527488-C-T is Benign according to our data. Variant chr7-5527488-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 1185839.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0104 (1583/152038) while in subpopulation AFR AF = 0.0366 (1518/41448). AF 95% confidence interval is 0.0351. There are 36 homozygotes in GnomAd4. There are 769 alleles in the male GnomAd4 subpopulation. Median coverage is 29. This position passed quality control check.
• BS2: High AC in GnomAd4 at 1583 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.*260G>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.*260G>A		3_prime_UTR	Exon 6 of 6	ENSP00000494750.1	P60709
	ACTB	ENST00000425660.5	TSL:1	n.*1051G>A		non_coding_transcript_exon	Exon 7 of 7	ENSP00000409264.1	G5E9R0
	ACTB	ENST00000425660.5	TSL:1	n.*1051G>A		3_prime_UTR	Exon 7 of 7	ENSP00000409264.1	G5E9R0

Frequencies

GnomAD3 genomes AF: 0.0103 AC: 1570 AN: 151920 Hom.: 35 Cov.: 29

Gnomad AFR AF: 0.0364

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00289

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: 0.0000147

Gnomad OTH AF: 0.00959

GnomAD4 exome AF: 0.00123 AC: 529 AN: 428558 Hom.: 8 Cov.: 5 AF XY: 0.00104 AC XY: 235 AN XY: 226582

African (AFR) AF: 0.0345 AC: 408 AN: 11810

American (AMR) AF: 0.00260 AC: 43 AN: 16538

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 12018

East Asian (EAS) AF: 0.00 AC: 0 AN: 25124

South Asian (SAS) AF: 0.0000226 AC: 1 AN: 44308

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 24284

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1758

European-Non Finnish (NFE) AF: 0.0000260 AC: 7 AN: 269250

Other (OTH) AF: 0.00298 AC: 70 AN: 23468

GnomAD4 genome AF: 0.0104 AC: 1583 AN: 152038 Hom.: 36 Cov.: 29 AF XY: 0.0104 AC XY: 769 AN XY: 74290

African (AFR) AF: 0.0366 AC: 1518 AN: 41448

American (AMR) AF: 0.00289 AC: 44 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00 AC: 0 AN: 4812

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10562

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68012

Other (OTH) AF: 0.00949 AC: 20 AN: 2108

Alfa AF: 0.0137 Hom.: 1

Bravo AF: 0.0116

Asia WGS AF: 0.00318 AC: 12 AN: 3478

ClinVar

ClinVar submissions

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
BayesDel_noAF	Benign	-0.52
CADD	Benign	20
DANN	Benign	0.88
PhyloP100		1.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs11546906; hg19: chr7-5567119; COSMIC: COSV105237177; COSMIC: COSV105237177;